Terpenoids from Marine Sources: A Promising Avenue for New Antimicrobial Drugs

Abstract

Currently, there is an urgent need for new antibacterial and antifungal agents to combat the growing challenge of antibiotic resistance. As the largest ecosystem on Earth, the marine ecosystem includes a vast array of microorganisms (primarily bacteria and fungi), plants, invertebrates, and vertebrates, making it a rich source of various antimicrobial compounds. Notably, terpenoids, known for their complex structures and diverse bioactivities, are a significant and promising group of compounds in the battle against bacterial and fungal infections. In the past five years, numerous antimicrobial terpenoids have been identified from marine organisms such as bacteria, fungi, algae, corals, sea cucumbers, and sponges. This review article provides a detailed overview of 141 terpenoids with antibacterial and/or antifungal properties derived from marine organisms between 2019 and 2024. Terpenoids, a diverse group of natural organic compounds derived from isoprene units, are systematically categorized based on their carbon skeleton structures. Comprehensive information is provided about their names, structures, biological sources, and the extent of their antibacterial and/or antifungal effectiveness. This review aims to facilitate the rapid identification and development of prospective antimicrobials in the pharmaceutical sector.

1. Introduction

Antibiotics represent one of the most effective drugs for developing infections in humans and animals. Their extensive use is due to their broad spectrum of activity, which includes inhibiting the biosynthesis of the bacterial cell wall, disrupting the integrity of the cell membrane, suppressing the synthesis of nucleic acids and proteins, and interfering with metabolic processes [1].

Unfortunately, the advent of antibiotics has been accompanied by the escalating problem of antimicrobial drug resistance. In addition to inherent resistance, bacteria can acquire resistance to specific antimicrobial agents by transferring genetic material that confers resistance. To date, some of the most commonly observed strategies of bacterial resistance include modification of antibiotic target sites, increased cell wall permeability to antibiotics, active expulsion of antibiotics from the cell (known as efflux systems), and enzymatic inactivation [2]. Antibiotic resistance is a significant global public health concern, with an estimated 1.27 million deaths worldwide attributed to it [3]. It is projected that by 2050, the global death toll due to antibiotic resistance could reach 10 million per year, up from the current estimate of 700,000 deaths per year [4]. The widespread use of antibiotics in clinical and community settings and livestock and crop production is considered one of the main drivers of antimicrobial resistance [5,6,7]. The widespread use of antibiotics in clinical and community settings and livestock and crop production is considered one of the main drivers of antimicrobial resistance. Thus, it is necessary to improve the appropriate use of antibiotics and reduce unnecessary use. The World Health Organization has identified the ESKAPE pathogens—vancomycin-resistant Enterococcus faecalis (VRE), methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae (K. pneumoniae), Acinetobacter baumannii (A. baumannii), Pseudomonas aeruginosa (P. aeruginosa), and vancomycin-resistant Enterobacter—as those with increasing multidrug resistance. Additionally, in epidemiology, Escherichia coli (E. coli), penicillin-resistant Streptococcus pneumoniae (PRSP), and extensively drug-resistant (XDR) Mycobacterium tuberculosis (M. tuberculosis) are well-known and significant multidrug-resistant bacteria [8,9,10]. The urgent need for new types of antibiotics to combat these pathogens highlights the importance of discovering and developing new antibacterial products for human, animal, agricultural, food, and environmental health [11].

It is well recognized that the marine ecosystem, the largest and most significant ecosystem on Earth, boasts immense biodiversity, including organisms ranging from nanoscale microorganisms to whales [12]. The marine environment offers a higher likelihood of discovering new antibacterial drug leads than terrestrial environments, making it a promising source for developing new antibiotics. Various marine organisms, such as bacteria, fungi, algae, corals, sea cucumbers, and sponges, have been explored for isolating antibacterial and antifungal bioactive compounds [13].

Terpenoids, significant both as natural products from terrestrial microorganisms and as metabolites in the ocean, are key candidates in the fight against microbial infections [14]. This review article provides a comprehensive account of 143 terpenoids identified between 2019 and 2024, with antibacterial and/or antifungal activities, sourced from a diverse array of marine organisms, including bacteria, fungi, algae, corals, sea cucumbers, and sponges. It details the names, structures, biological origins, and the compounds’ effectiveness against drug-resistant pathogens (most entries include the minimum inhibitory concentration (MIC) values against test bacterial and/or fungal strains). Additionally, certain compounds’ structure–activity relationships (SARs) were analyzed based on the magnitude of antimicrobial activity. The structures of these compounds are depicted in Figures 2–5, while the remaining information is presented in Tables 1–8. Figure 1 illustrates the analysis of statistical data. This review aims to facilitate and accelerate the identification and development of potentially innovative antimicrobial compounds to advance new pharmaceutical options.

2. Chemical Constitution

Terpenes are a diverse group of natural products synthesized from repeating units of isoprene. This class includes various compounds, such as monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and triterpenoids (C30). Frequent skeletal rearrangements within these structures often deviate from the typical head-to-tail arrangement of isoprene units, introducing a significant degree of diversity to the terpenoid framework [13,15]. This review encompasses 141 antimicrobial terpenoids, including 48 sesquiterpenoids, 39 diterpenoids, 20 triterpenoids, and 34 meroterpenoids.

2.1. Sesquiterpenoids (1–48)

Sesquiterpenes are characterized by their basic carbon skeleton, which includes 15 carbon atoms arranged in three isoprene units. This section introduces 48 sesquiterpenoid compounds, including one linear sesquiterpenoid, three nardosinane-type sesquiterpenes, three neolemnane sesquiterpenes, one aristolane-type sesquiterpenoid, two drimane sesquiterpenes, and four each of carotane-style, merosesquiterpenoids, and three illudalane-style sesquiterpenoid. Additionally, there are eleven bisabolane-type sesquiterpenoids and eight sesquiterpene-derived compounds, such as sesquiterpene hydroquinones and sesquiterpene glycosides, and seven unclassified sesquiterpenoids.

The chemical structures of sesquiterpenoids 1–48 are depicted in Figure 2, while the remaining information, including names and marine sources, is presented in

Table 1. Names, classes, skeletons, and marine sources of sesquiterpenoids (1–48).

No.	Names	Classes	Marine Sources	Ref.
1	Chermesiterpenoid D	Linear Sesquiterpenoid	Magellan Seamount-Derived fungus Penicillium rubens AS-130	[16]
2	12-O-acetyl-nardosinan-6-en-1-one	Nardosinane Sesquiterpene	Octocoral Rhytisma fulvum fulvum	[17]
3	6β-acetyl-1(10)-α-13-nornardosin-7-one			[17]
4	6α-acetyl-1(10)-α-13-nornardosin-7-one			[17]
5	Lineolemnene E	Neolemnane Sesquiterpene	Soft coral Lemnalia sp.	[18]
6	Lineolemnene F
7	Lineolemnene G
8	2-acetoxy-aristolane	Aristolane Sesquiterpenoid	Soft coral Lemnalia sp.	[18]
9	Lactone purpuride D	Drimane Sesquiterpene	The marine-derived Penicillium sp. ZZ1283	[19]
10	Astellolide Q	Drimane Sesquiterpene	The marine-derived fungus Penicillium sp. N-5	[20]
11	Byssocarotin A	Carotane Sesquiterpenoid	Macroalga-Derived Algicolous Fungus Penicillium rubens RR-dl-2-13	[21]
12	Byssocarotin B			[21]
13	Byssocarotin C			[21]
14	Byssocarotin D			[21]
15	Alcyopterosin T	Illudalane Sesquiterpenoid	Octocoral Alcyonium sp.	[22] [22]
16	Alcyopterosin U			[22]
17	Alcyopterosin V			[22]
18	Nakijiquinone V	Sesquiterpenoid Aminoquinone	Indonesian marine Dactylospongia elegans sponge	[23]
19	Illimaquinone	Merosesquiterpenoid	Indonesian marine Dactylospongia elegans sponge	[23]
20	Smenospongine			[23]
21	Dyctioceratine C			[23]
22	Plakordiol A	Bisabolane Phenolic Sesquiterpenoid	The marine sponge Plakortis simplex	[24]
23	Plakordiol B			[24]
24	Plakordiol C			[24]
25	Plakordiol D			[24]
26	(7R, 10R)-hydroxycurcudiol			[24]
27	(7R, 10S)-hydroxycurcudiol			[24]
28	Sydonic acid	Bisabolene Sesquiterpenoid	Aspergillus versicolor AS-212	[25]
29	(S)-(+)-11-dehydrosydonic acid			[25]
30	(−)-10-hydroxysydonic acid			[25]
31	hydroxysydonic acid			[25]
32	Peniciaculin B			[25]
33	Xishaeleganins A	Sesquiterpenoid Hydroquinone	Xisha Marine Sponge Dactylospongia elegans	[26]
34	Xishaeleganins B			[26]
35	Xishaeleganins C			[26]
36	Xishaeleganins D			[26]
37	Agelasidine G	Sesquiterpenoid Alkaloid	Sponge Agelas nakamurai	[27]
38	Agelasidine H			[27]
39	Agelasidine I			[27]
40	Malfilanol C	Sesquiterpenoid	The deep-sea-derived fungus Aspergillus puniceus A2	[28]
41	Trichoacorside A	Sesquiterpene Glycoside	Red Alga Laurencia obtuse -Derived Endophytic Fungus Trichoderma longibrachiatum EN-586	[29]
42	Citreobenzofuran D	Sesquiterpenoid	Mangrove-Derived Fungus Penicillium sp. HDN13-494	[30]
43	Citreobenzofuran E			[30]
44	Citreobenzofuran F			[30]
45	Phomenone A			[30]
46	Phomenone B			[30]
47	O8-ophiocomane	Sesquiterpenoid	Brittle star; Ophiocoma dentata	[31]
48	O7-ophiocomane			[31]

.

2.1.1. Linear Sesquiterpenoid

Chermesiterpenoid D (1), a new linear sesquiterpenoid, was isolated and identified from the fungus Penicillium rubens AS-130, which originates from the Magellan Seamount. The elucidation of its structure was achieved through nuclear magnetic resonance (NMR) and mass spectroscopic (MS) data analysis. The determination of its absolute configuration was accomplished by employing a synergistic approach of quantum mechanics (QM)-NMR and time-dependent density functional theory (TDDFT) computational methods [16].

2.1.2. Nardosinane-Type Sesquiterpenes

Three undescribed nardosinane-type sesquiterpenes, including 12-O-acetyl-nardosinan-6-en-1-one (2), 6β-acetyl-1(10)-α-13-nornardosin-7-one (3), and 6α-acetyl-1(10)-α-13-nornardosin-7-one (4), were isolated from the alcyonacean soft coral Rhytisma fulvum fulvum. Their chemical structures were elucidated based on 1D, 2D NMR, and MS spectral data [17].

2.1.3. Neolemnane Sesquiterpenes and Aristolane-Type Sesquiterpenoids

Three novel neolemnane sesquiterpenes, designated as Lineolemnenes E, F, and G (5–7), along with a new aristolane-type sesquiterpenoid, 2-acetoxy-aristolane (8), have been characterized. Their structural elucidation was achieved through comprehensive spectroscopic analyses coupled with the comparison of experimental and calculated electronic circular dichroism (ECD) data [18].

2.1.4. Drimane Sesquiterpenes

A marine-derived Penicillium sp. ZZ1283 yielded a novel drimane sesquiterpene lactone, purpuride D (9). The structure of purpuride D was elucidated through a multifaceted approach that included high-resolution electrospray ionization mass spectrometry (HRESIMS), NMR spectroscopic analyses, single-crystal X-ray diffraction, and ECD calculations [19]. Additionally, another drimane sesquiterpenoid, astellolide Q (10), was isolated from the culture of the marine fungus Penicillium sp. N-5. Its structure was also determined by a combination of spectroscopic methods, including MS, NMR, ECD, and X-ray diffraction [20].

2.1.5. Carotane-Style Sesquiterpenoids

Byssocarotins A−D (11–14), four new carotane-style sesquiterpenoids, were obtained from a macroalga-associated strain (RR-dl-2-13) of the fungus Byssochlamys spectabilis. These isolates were identified through an integrated application of various spectroscopic techniques, encompassing MS, NMR, ECD, and X-ray diffraction [21].

2.1.6. Illudalane Sesquiterpenoids

From an Antarctic deep-water octocoral, four bioactive compounds were successfully isolated, comprising three illudalane sesquiterpenoids: Alcyopterosin T (15), Alcyopterosin U (16), and Alcyopterosin V (17). The structural characterization of these novel entities was accomplished by employing a thorough suite of 1D and 2D NMR analytical techniques [22].

2.1.7. Merosesquiterpenoids

Four merosesquiterpenoids, including a new sesquiterpenoid aminoquinone known as nakijiquinone V (18), were identified from the Indonesian marine sponge Dactylospongia elegans. Additionally, illimaquinone (19), smenospongine (20), and dyctioceratine C (21) were also found. The structure of compound 18 was elucidated by 1D and 2D NMR as well as by liquid chromatography HRESIMS data analysis [23].

2.1.8. Bisabolane-Type Phenolic Sesquiterpenoids

From the South China Sea marine sponge Plakortis simplex, a collection of six novel bisabolane-type phenolic sesquiterpenoids was successfully isolated, including plakordiols A to D (22–25), (7R, 10R)-hydroxycurcudiol (26), and (7R, 10S)-hydroxycurcudiol (27). These compounds were extracted from the methanolic extract of Plakortis simplex through a series of reversed-phase chromatography and RP-HPLC separation techniques. The elucidation of their structures was facilitated by MS and NMR spectroscopy. Furthermore, compounds 22–27’s stereochemical configurations were determined by combining coupling constant analysis, NOESY correlations, and applying the modified Mosher’s method [24].

Bisabolene derivatives, designated as compounds 28–31, and a bisabolene dimer (32), were successfully isolated and characterized from Aspergillus versicolor AS-212, an Endozoic Fungus associated with Deep-Sea Coral of Magellan Seamounts. The chemical structures were ascertained through a comprehensive analysis of spectroscopic data, X-ray crystallography, specific rotation, ECD calculations, and spectral comparison [25].

2.1.9. Sesquiterpene-Derived Compounds

Four new sesquiterpene hydroquinones, named xishaeleganins A–D (compounds 33–36), have been successfully isolated from the Xisha marine sponge Dactylospongia elegans (family Thorectida). Their structures were determined through a thorough examination using spectroscopic methods, ECD computations, and corroboration with spectral data documented in existing literature [26].

Three novel 2-guanidinoethanesulfonyl sesquiterpene analogs of (−)-agelasidine A, designated agelasidines G–I numbered compounds 37–39, were isolated from a marine sponge Agelas nakamurai, which was collected in Orchid Island. The absolute configurations for compounds 37–39 were ascertained by applying computational NMR data, the statistical DP4+ protocol, and correlating their experimental optical rotations with values predicted by B3LYP calculations [27].

Malfilanol C (40), a novel sesquiterpenoid, was first identified from the Aspergillus genus through its successful isolation from the rice solid-state fermentation products of the deep-sea-derived fungus Aspergillus puniceus A2. Its structure was elucidated based on comprehensive spectroscopic analysis, including HRESIMS and NMR, and comparing experimental and calculated ECD spectra to determine the absolute configuration [28].

A sesquiterpene glycoside, trichoacorside A (41), was isolated and identified from the culture extract of Trichoderma longibrachiatum EN-586, an endophytic fungus, obtained from the marine red alga Laurencia obtuse. The structures were deciphered from NMR and MS data, with absolute configurations confirmed through X-ray crystallography, derivatization, and DP4+ analysis [29].

2.1.10. Others Sesquiterpenoids

From the cultured mangrove-derived fungus Penicillium sp. HDN13-494, five novel sesquiterpenoids have been isolated: citreobenzofurans D to F (42–44) and phomenones A to B (45–46). Their structures were identified through comprehensive spectroscopic analysis, HRESIMS, and ECD calculations. Additionally, the absolute structure of compound 43 was confirmed by single-crystal X-ray diffraction [30].

Two novel sesquiterpenoids, identified as O8-ophiocomane (47) and O7-ophiocomane (48), have been successfully isolated from the brittle star Ophiocoma dentata, locally sourced from the Red Sea coast of Egypt. The structures were determined using 1D and 2D NMR, FT-IR, and MS [31].

2.2. Diterpenoids (49–87)

Diterpenoids are a class of naturally occurring secondary metabolites with complex and diverse structures and biological activities, composed of 20 carbon atoms with extensive skeletal rearrangements [32]. This section presents 39 diterpenoid compounds, encompassing three 5,5,6,6,5-pentacyclic spongian diterpenes, nine indole diterpenes, one indole diterpene amino acid conjugate, three membrane diterpenes, two cyclopiane diterpenes, three diterpene alkaloids, six bicyclic diterpene glycosides, seven biflorane-type diterpenoids, and four decalin-type bicyclic diterpenes. The chemical structures of diterpenoids 49–87 are depicted in Figure 3, while the remaining information, including names and marine sources, is presented in

Table 2. Names, classes, skeletons, and marine sources of diterpenoids (50–88).

No.	Names	Classes	Marine Sources	Ref.
49	Spongenolactone A	5,5,6,6,5-Pentacyclic Spongian Diterpenes	Red Sea sponge Spongia sp.	[33]
50	Spongenolactone B			[33]
51	Spongenolactone C			[33]
52	Janthinellumine A	Indole Diterpene	Co-culturing the marine-derived fungi Penicillium janthinellium with Paecilomyces formosus	[34]
53	Janthinellumine B			[34]
54	Janthinellumine C			[34]
55	Janthinellumine D			[34]
56	Janthinellumine E			[34]
57	Janthinellumine F			[34]
58	Janthinellumine G			[34]
59	Janthinellumine H			[34]
60	Janthinellumine I			[34]
61	Noonindole A	Indole Diterpene Amino Acid	Fungus Aspergillus noonimiae CMB-M0339	[35]
62	Nephthecrassocolide A	Cembrane Diterpene	Bornean soft coral Nephthea sp.	[36]
63	Nephthecrassocolide B			[36]
64	6-Acetoxy Nephthenol Acetate			[36]
65	4-Hydroxyleptosphin C	Cyclopiane Diterpene	The marine sediment-derived fungus Penicillium antarcticum KMM 4670	[37]
66	13-Epi-Conidiogenone F			[37]
67	(+)-8-Epiagelasine T	Diterpene Alkaloid	Agelas citrina Sponge	[38]
68	(+)-10-Epiagelasine B			[38]
69	(+)-12-Hydroxyagelasidine C			[38]
70	Lemnabourside E	Bicyclic Diterpene Glycoside	Soft coral Lemnalia bournei	[39]
71	Lemnabourside F			[39]
72	Lemnabourside G			[39]
73	Lemnadiolbourside A			[39]
74	Lemnadiolbourside B			[39]
75	Lemnadiolbourside C			[39]
76	Biofloranate E	Biflorane-Type Diterpenoid	Soft coral Lemnalia bournei	[40]
77	Biofloranate F			[40]
78	Biofloranate G			[40]
79	Biofloranate H			[40]
80	Biofloranate I			[40]
81	Lemnabourside H	Bicyclic Diterpene Glycoside	Soft coral Lemnalia bournei	[40]
82	Lemnabourside I			[40]
83	Biofloranate A	Decalin-Type Bicyclic Diterpene	Soft coral Lemnalia sp.	[18]
84	Biofloranate B			[18]
85	Biofloranate C			[18]
86	Biofloranate D			[18]
87	Cneorubin K	Aromadendrane-Type Diterpenoid	Soft coral Lemnalia sp.	[18]

.

2.2.1. 5,5,6,6,5-Pentacyclic Spongian Diterpenes

From a Red Sea sponge specimen identified as Spongia sp., three novel 5,5,6,6,5-pentacyclic spongian diterpenes, designated Spongenolactones A–C and numbered 49–51, have been isolated. Their structures were determined through comprehensive spectroscopic analysis, and the absolute configurations were ascertained by comparing experimental circular dichroism (CD) spectra with calculated ECD spectra [33].

2.2.2. Indole Diterpenes

Nine novel indole diterpenes, designated as Janthinellumine A through I and numbered 52–60, were isolated from the co-culture of two marine-derived fungi, Penicillium janthinellium and Paecilomyces formosus. The chemical structures and absolute configurations were determined using extensive spectroscopic data and computational ECD and vibrational circular dichroism (VCD) methods [34].

A rare indole diterpene amino acid conjugate, noonidole A (61), was derived from the marine fungus Aspergillus sp. CMB-M0339 (identified as Aspergillus noonimiae). Its structure was determined through MS spectroscopy and X-ray crystallography [35].

2.2.3. Cembrane Diterpenes

Three novel cembrane diterpenes, Nephthecrassocolides A and B (62–63), along with 6-acetoxynephthenol acetate, have been isolated from a population of the marine organism Nephthea sp. Their structures were determined using spectroscopic methods, including MS, NMR, and nuclear Overhauser effect spectroscopy (NOESY) [36].

2.2.4. Cyclopiane Diterpenes

Two novel cyclopiane diterpenes, 4-Hydroxyleptosphin C (65) and 13-epi-conidiogenone F (66), have been isolated from the marine sediment-derived fungus Penicillium antarcticum KMM 4670. Their absolute configurations were confirmed by the modified Mosher method and ECD spectrum calculations [37].

2.2.5. Diterpene Alkaloids

Three new diterpene alkaloids, (+)-8-epiagelasine T (67), (+)-10-epiagelasine B (68), and (+)-12-hydroxyagelasidine C (70), have been isolated from the sponge Agelas citrina, which was collected along the coasts of the Yucatan Peninsula. Their structures were identified through NMR spectroscopy, HRESIMS, and literature comparison [38].

2.2.6. Bicyclic Diterpene Glycosides

From the soft coral Lemnalia bournei, six new bicyclic diterpene glycosides—lemnaboursides E to G (70–72) and lemnadiolboursides A to C (73–75)—were meticulously isolated and characterized. Their structures were determined using spectroscopy (MS, NMR, heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC), HRESIMS), ECD analysis, optical rotation, and literature data comparison [39].

2.2.7. Biflorane-Type Diterpenoids

A series of novel secondary metabolites, comprising five new biflorane-type diterpenoids designated as biofloranates E through I (76–80) and two new bicyclic diterpene glycosides named lemnaboursides H through I (81–82), have been successfully isolated from the soft coral Lemnalia bournei, collected from the South China Sea. Their chemical structures and stereochemistry were identified using various spectroscopic techniques and TDDFT ECD calculations and were confirmed by comparing them with reported values [40].

2.2.8. Decalin-Type Bicyclic Diterpenes

Four novel decalin-type bicyclic diterpenes, designated Biofloranates A to D (83–86), along with a new aromadendrane-type diterpenoid (87), have been successfully isolated from the soft coral Lemnalia sp., collected from the South China Sea. The new compounds’ structures were determined using NMR, Mosher’s method, and ECD analysis [18].

2.3. Triterpenoids (88–107)

Triterpenoids are a class of ubiquitous natural organic compounds in nature, consisting of six isoprene units, totaling 30 carbon atoms. This section introduces 20 triterpenoid compounds, including details on the names, sources, and structures of the nine isomalabaricane terpenoids and eleven fusicane-type nortriterpenoids. The chemical structures of triterpenoids 88–107 are depicted in Figure 4, while the remaining information, including names and marine sources, is presented in

Table 3. Names, classes, skeletons, and marine sources of triterpenoids (88–107).

No.	Names	Classes	Marine Sources	Ref.
88	13-(E)-geoditin A	Isomalabaricane Terpenoid	Sponge Rhabdastrella globostellata	[41]
89	13-(E)-isogeoditin B			[41]
90	3-Acetylstelliferin D			[41]
91	29-Acetylstelliferin D			[41]
92	Hainanstelletin A			[41]
93	Hainanstelletin B			[41]
94	23,24-Ene-25-hydroxystelliferin D			[41]
95	25,26-Ene-24-hydroxystelliferin D			[41]
96	Hainanstelletin C			[41]
97	Implifusidic acid A	Fusidane-Type Nortriterpenoid	The marine-derived fungus Simplicillium sp. SCSIO 41513.	[42]
98	Implifusidic acid B			[42]
99	Implifusidic acid C			[42]
100	Implifusidic acid D			[42]
101	Implifusidic acid E			[42]
102	Implifusidic acid F			[42]
103	Implifusidic acid G			[42]
104	Implifusidic acid H			[42]
105	Implifusidic acid I			[42]
106	Implifusidic acid J			[42]
107	Implifusidic acid K			[42]

.

2.3.1. Isomalabaricane Terpenoids

Nine novel isomalabaricane terpenoids, numbered 88–96, have been successfully isolated from the sponge Rhabdastrella globostellata collected from Ximao Island. The structures were determined using spectroscopic methods, including MS, NMR, HMBC, and ECD, and by comparing them with known compounds’ data [41].

2.3.2. Fusicane-Type Nortriterpenoids

Eleven novel fusicane-type nortriterpenoids, named Implifusidic acids A–K and numbered 97–107, have been successfully isolated from the marine-derived fungus Simplicillium sp. SCSIO 41513. Their structures were identified through spectroscopy, and the absolute configurations were confirmed by ECD calculations, spectral comparison, and X-ray diffraction [42].

2.4. Meroterpenoids (108–141)

Meroterpenoids are hybrid secondary metabolites from mixed biosynthetic pathways, partially derived from terpenoid substrates. These compounds, produced widely by bacteria, algae, plants, and animals, exhibit remarkable chemical diversity by combining terpenoid frameworks with polyketides, alkaloids, phenols, and amino acids [43,44,45]. The chemical structures of meroterpenoids 108–141 are depicted in Figure 5, while the remaining information, including names, marine sources, and results of antibacterial activity assays, is presented in

Table 4. Names, classes, skeletons, and marine sources of meroterpenoids (108–141).

No.	Names	Classes	Marine Sources	Ref.
108	Chermesin E	Meroterpenoid	Red alga-derived endophytic Penicillium chermesinum EN-480	[46]
109	Chermesin F			[46]
110	Chermesin G			[46]
111	Chermesin H			[46]
112	Taladrimanin A	Drimane-Type Meroterpenoid	Fungus Talaromyces sp. HM6-1–1	[47]
116	Taladrimanin B	Meroterpenoid	The marine-derived fungus Talaromyces sp. M27416	[48]
119	Chevalone H	α-Pyrone Meroterpenoid	Gorgonian coral-derived fungus Aspergillus hiratsukae SCSIO 7S2001	[49]
120	Chevalone I			[49]
121	Chevalone J			[49]
122	Chevalone K			[49]
123	Chevalone L			[49]
124	Chevalone M			[49]
125	Asnovolin C 5′6′-dehydrohydrogen	Spiromeroterpenoid	Conch snail-derived fungus Trametes sp. ZYX-Z-16	[50]
126	Asnovolin C			[50]
127	Chermesin A			[50]
128	Chrodrimanin E			[50]
129	Chrodrimanin H			[50]
130	Thailandolide B			[50]
131	Asnovolin H			[50]
132	Asnovolin I			[50]
133	Hemiacetalmeroterpenoid A	Andrastin-Type Meroterpenoid	The marine-derived fungus Penicillium sp. N-5	[20]
134	Hemiacetalmeroterpenoid B			[20]
135	Hemiacetalmeroterpenoid C			[20]
136	Merochlorin G	Chlorinated Meroterpenoid	Marine sediment-derived bacterium strain Streptomyces sp. CNH-189	[51]
137	Merochlorin H			[51]
138	Merochlorin I			[51]
139	Merochlorin J			[51]
140	Aspergillactone	Meroterpenoid	The marine fungus Aspergillus sp. CSYZ-1	[52]
141	Oxalicine C	Meroterpenoid-Type Alkaloid	The marine-algal-derived endophytic fungus Penicillium chrysogenum XNM-12	[53]

.

Four novel meroterpenoids, designated as chermesins E–H (108–111), were successfully isolated from Penicillium chermesinum EN-480, an endophyte derived from the marine red alga. The structures were ascertained using HRESIMS and NMR, with absolute configurations verified through NOESY, X-ray diffraction, and ECD cotton effect analysis [46].

2.4.1. Drimane-Type Meroterpenoid

The first drimane-type meroterpenoid featuring a C10 polyketide unit with an 8R-configuration, named taladrimanin A (112), has been isolated alongside three biogenetically related compounds (113–115) from the marine-derived fungus Talaromyces sp. HM6-1–1 [47]. After two years, three new drimane-type meroterpenoids, designated as Taladrimanin B to D and numbered 116–118, have been successfully isolated from the marine-derived fungus Talaromyces sp. M27416 [48]. The planar structure of 112 was identified using HRESIMS and NMR. Its relative configuration was deduced through quantum chemical NMR calculations of potential isomers and the DP4+ method. X-ray diffraction confirmed the relative and absolute configurations. Compound 116’s structure was elucidated by HRESIMS and NMR, with configuration confirmed by quantum chemical analysis and the DP4+ method and verified by X-ray crystallography. ECD calculations established the absolute configuration of 116, while comparative NMR and ECD analyses determined those of 117 and 118.

2.4.2. α-Pyrone Meroterpenoids

Six new α-pyrone meroterpenoids, designated as chevalones H–M and numbered 119–124, have been successfully isolated from Aspergillus hiratsukae SCSIO 7S2001, a fungus derived from the gorgonian coral collected at Mischief Reef in the South China Sea. The structures and absolute configurations were determined by spectroscopy and X-ray diffraction [49].

2.4.3. Spiromeroterpenoids

The chemical exploration of the ethyl acetate (EtOAc) extract derived from the fermentation broth of the marine fungus Trametes sp. ZYX-Z-16 yielded eight meroterpenoids, numbered 125–132, among which two novel spiromeroterpenoids, named asnovolin H (131) and asnovolin I (132), were identified. The structures of 131 and 132 were identified through 1D and 2D NMR, HRESIMS, and ECD spectral analysis [50].

2.4.4. Andrastin-Type Meroterpenoids

In addition to compound 10, three andrastin-type meroterpenoids, identified as Hemiacetalmeroterpenoids A to C (133–135), were isolated from the marine-derived fungus Penicillium sp. N-5. Its structure was also determined by a combination of spectroscopic methods, including MS, NMR, ECD, and X-ray diffraction [20].

2.4.5. Chlorinated Meroterpenoids

From the cultivation of the marine sediment-derived bacterium strain Streptomyces sp. CNH-189, four novel chlorinated meroterpenoids, identified as merochlorins G through J (136–139), have been successfully isolated. The planar structures of compounds 137−140 were deduced from MS, ultraviolet-visible spectroscopy, and NMR data. Their relative configurations were inferred from nuclear Overhauser effect (NOE) data, and absolute configurations were confirmed by comparing ECD spectra with known models and DP4 calculations [51].

2.4.6. 3,5-Dimethylorsellinic Acid-Based Meroterpenoid

A chemical investigation of the extracts from the fungus Aspergillus sp. CSYZ-1 has led to the identification of aspergillactone (140), a novel 3,5-dimethylorsellinic acid-based meroterpenoid. NMR and mass spectrometry confirmed the structure and relative configuration of 140. Its absolute configuration was ascertained through TDDFT calculations and comparison with experimental ECD spectra [52].

2.4.7. Meroterpenoid-Type Alkaloid

Oxalicine C (141), a novel meroterpenoid-type alkaloid, has been isolated from the endophytic fungus Penicillium chrysogenum XNM-12, derived from marine algae. The planar structure of compound 141 was elucidated through spectroscopic analyses comprising ultraviolet–visible spectroscopy, 1D and 2D NMR, and HRESIMS. Its stereochemical configuration was determined by comparing experimental and calculated ECD spectra [53].

3. Antibacterial and/or Antifungal Activity

3.1. Sesquiterpenoids

This section provides a detailed account of the antimicrobial activities of 48 sesquiterpenoid compounds, with further details presented in

Table 5. Antibacterial and/or antifungal activities of sesquiterpenoids (1–48).

No.	Test Strains	Activity	Bioassays	Ref.
1	MRSA	Antibacterial	MIC = 64 µg/mL	[16]
2	B. cereus	Antibacterial	diameters of inhibition zone 6 ± 0.03 mm (50 µg/mL)	[17]
	S. aureus		diameters of inhibition zone 5 ± 0.00 mm (50 µg/mL)
	E. coli		negative
	Pseudomonas sp.		diameters of inhibition zone 4 ± 0.00 mm (50 µg/mL)
3	B. cereus	Antibacterial	diameters of inhibition zone 6 ± 0.00 mm (100 µg/mL)	[17]
	S. aureus		diameters of inhibition zone 5 ± 0.00 mm (100 µg/mL)
	E. coli		diameters of inhibition zone 4 ± 0.00 mm (100 µg/mL)
	Pseudomonas sp.		negative
4	B. cereus	Antibacterial	diameters of inhibition zone 6 ± 0.00 mm (100 µg/mL)	[17]
	S. aureus		diameters of inhibition zone 5 ± 0.00 mm (100 µg/mL)
	E. coli		diameters of inhibition zone 4 ± 0.00 mm (100 µg/mL)
	Pseudomonas sp.		negative
5	S. aureus	Antibacterial	MIC > 128 µg/mL	[18]
	B. cereus
6	S. aureus	Antibacterial	MIC > 128 µg/mL	[18]
	B. cereus
7	S. aureus	Antibacterial	MIC > 128 µg/mL	[18]
	B. cereus
8	S. aureus	Antibacterial	MIC > 128 µg/mL	[18]
	B. cereus
9	MRSA	Antibacterial	MIC = 4 µg/mL	[19]
	E. coli		MIC = 3 µg/mL
	C. albicans	Antifungal	MIC = 8 µg/mL
10	MRSA	Antibacterial	MIC >50 µg/mL	[20]
	B. cereus
	P. italicum	Antifungal	MIC = 25 µg/mL
	C. gloeosporioides
11	V. anguillarum	Antibacterial	diameters of inhibition zone 6.3 ± 0.6 mm (50 µg/disk)	[21]
	V. harveyi		negative
	V. parahaemolyticus		diameters of inhibition zone 6.7 ± 0.6 mm (50 µg/disk)
12	V. anguillarum	Antibacterial	diameters of inhibition zone 6.7 ± 0.6 mm (50 µg/disk)	[21]
	V. harveyi		negative
	V. parahaemolyticus		diameters of inhibition zone 7.3 ± 0.6 mm (50 µg/disk)
13	V. anguillarum	Antibacterial	negative	[21]
	V. harveyi		negative
	V. parahaemolyticus		diameters of inhibition zone 7.3 ± 0.6 mm (50 µg/disk)
14	V. anguillarum	Antibacterial	negative	[21]
	V. harveyi		negative
	V. parahaemolyticus		diameters of inhibition zone 6.7 ± 0.6 mm (50 µg/disk)
15	ESKAPE	Inactive	inactive against the ESKAPE	[22] [22]
16	ESKAPE	Inactive	inactive against the ESKAPE	[22]
17	C. difficile	Antibacterial	MIC 8.1 µg/mL	[22]
	ESKAPE		inactive against the ESKAPE
18	B. megaterium DSM32	Inactive	inactive against B. Megaterium DSM32	[23]
	M. luteus ATCC 4698		inactive against M. Luteus ATCC 4698
19	B. megaterium DSM32	Antibacterial	MIC = 32 µg/mL	[23]
	M. luteus ATCC 4698
20	B. megaterium DSM32	Antibacterial	MIC = 32 µg/mL	[23]
	M. luteus ATCC 4698
21	B. megaterium DSM32	Antibacterial	MIC = 32 µg/mL	[23]
	M. luteus ATCC 4698		MIC = 64 µg/mL
22	S. aureus ATCC 25923	Antibacterial	MIC > 64 µg/mL	[24]
	MRSA ATCC 43300
	A. baumannii ATCC19606
	P. aeruginosa (clinical)
	VRE CD27
23	S. aureus ATCC 25923	Antibacterial	MIC > 64 µg/mL	[24]
	MRSA ATCC 43300
	A. baumannii ATCC19606
	P. aeruginosa (clinical)
	VRE CD27
24	S. aureus ATCC 25923	Antibacterial	MIC > 64 µg/mL	[24]
	MRSA ATCC 43300
	A. baumannii ATCC19606
	P. aeruginosa (clinical)
	VRE CD27
25	S. aureus ATCC 25923	Antibacterial	MIC > 64 µg/mL	[24]
	MRSA ATCC 43300
	A. baumannii ATCC19606
	P. aeruginosa (clinical)
	VRE CD27
26	S. aureus ATCC 25923	Antibacterial	MIC > 64 µg/mL	[24]
	MRSA ATCC 43300
	A. baumannii ATCC19606
	P. aeruginosa (clinical)
	VRE CD27
27	A. baumannii ATCC19606	Antibacterial	diameters of inhibition zone 5.0 ± 0.6 mm, but MIC > 64 µg/mL	[24]
28	V. harveyi	Antibacterial	MIC = 15.0 µg/mL	[25]
	V. Parahaemolyticus
	C. Gloeosporioides	Antifungal	MIC = 120.3 µg/mL
29	V. harveyi	Antibacterial	MIC = 15.2 µg/mL	[25]
	V. Parahaemolyticus		MIC = 121.2 µg/mL
	C. Gloeosporioides	Antifungal	MIC = 121.2 µg/mL
30	V. harveyi	Antibacterial	MIC = 28.4 µg/mL	[25]
	V. Parahaemolyticus		MIC = 113.5 µg/mL
	C. Gloeosporioides	Antifungal	MIC > 200 µg/mL
31	V. harveyi	Antibacterial	MIC > 200 µg/mL	[25]
	V. Parahaemolyticus
	C. Gloeosporioides	Antifungal	MIC > 200 µg/mL
32	V. harveyi	Antibacterial	MIC > 200 µg/mL	[25]
	V. Parahaemolyticus		MIC = 64 µg/mL
	C. Gloeosporioides	Antifungal	MIC > 200 µg/mL
33	S. aureus USA300 LAC	Inactive	inactive against S. aureus USA300 LAC	[26]
	S. pyogenes ATCC 12344		inactive against S. pyogenes ATCC 12344
	E. Faecium Efm-HS0649		inactive against E. Faecium Efm-HS0649
34	S. aureus USA300 LAC	Antibacterial	MIC = 1.5 µg/mL	[26]
	S. pyogenes ATCC 12344		MIC = 1.5 µg/mL
	E. Faecium Efm-HS0649		MIC = 3.0 µg/mL
35	S. aureus USA300 LAC	Antibacterial	MIC = 11.1 µg/mL	[26]
	S. pyogenes ATCC 12344		MIC = 2.8 µg/mL
	E. Faecium Efm-HS0649		MIC = 5.6 µg/mL
36	S. aureus USA300 LAC	Antibacterial	MIC > 186.0 µg/mL	[26]
	S. pyogenes ATCC 12344		MIC = 11.6 µg/mL
	E. Faecium Efm-HS0649		MIC > 186.0 µg/mL
37	B. subtilis	Antibacterial	diameters of inhibition zone 3.0 mm (25 mg/disk)	[27]
	E. coli
	K. Pneumoniae
	S. aureus
38	B. subtilis	Inactive	inactive against B. subtilis	[27]
	E. coli		inactive against E. coli
	K. Pneumoniae		inactive against K. Pneumoniae
	S. aureus		inactive against S. aureus
40	S. aureus ATCC 29213	Antibacterial	diameters of inhibition zone 8 mm (200 mg/disk)	[28]
41	E. coli	Antibacterial	MIC > 64 µg/mL	[29]
	MRSA		MIC = 64 µg/mL
	P. Aeruginosa		MIC > 64 µg/mL
	V. harveyi		MIC = 4 µg/mL
	V. Parahaemolyticus		MIC > 64 µg/mL
	A. Brassicae	Antifungal	MIC = 32 µg/mL
	C. Cornigerum		MIC = 64 µg/mL
	C. Gloeosporioides		MIC = 16 µg/mL
	C. Gloeosporioides Penz		MIC = 16 µg/mL
	Curvularia spicifera		MIC = 8 µg/mL
	F. Graminearum		MIC > 64 µg/mL
	F. Oxysporum		MIC = 32 µg/mL
	F. Oxysporum f. Sp. Radicis lycopersici		MIC = 32 µg/mL
	Fusarium proliferatum		MIC = 32 µg/mL
	P. Digitatum		MIC = 64 µg/mL
	P. Piricola Nose		MIC = 32 µg/mL
	A. hydrophilia		MIC = 64 µg/mL
42	B. subtilis	Antibacterial	MIC > 50 µg/mL	[30]
	A. Baumannii
	E. coil
	MRSA
	C. albicans	Antifungal	MIC > 50 µg/mL
43	B. subtilis	Antibacterial	MIC > 50 µg/mL	[30]
	A. Baumannii
	E. coil
	MRSA
	C. albicans	Antifungal	MIC > 50 µg/mL
44	B. subtilis	Antibacterial	MIC > 50 µg/mL	[30]
	A. Baumannii
	E. coil
	MRSA
	C. albicans	Antifungal	MIC > 50 µg/mL
45	B. subtilis	Antibacterial	MIC 6.25 µg/mL	[30]
	A. Baumannii		MIC > 50 µg/mL
	E. coil		MIC > 50 µg/mL
	MRSA		MIC > 50 µg/mL
	C. albicans	Antifungal	MIC > 50 µg/mL
46	B. subtilis	Antibacterial	MIC > 50 µg/mL	[30]
	A. Baumannii
	E. coil
	MRSA
	C. albicans	Antifungal	MIC > 50 µg/mL
47	P. Aeruginosa	Antibacterial	2.25 ± 0.04 mm AU	[31]
	E. Faecalis		1.36 ± 0.04 mm AU
48	P. Aeruginosa	Antibacterial	2.8 ± 0.05 mm AU	[31]
	E. Faecalis		1.8 ± 0.02 mm AU

.

Chermesiterpenoid D (1) demonstrated weak antibacterial activity, with MIC values for MRSA being 64 µg/mL [16]. Compounds 2–4 have exhibited against several Gram-positive (Bacillus cereus (B. cereus), Staphylococcus aureus (S. aureus)) and Gram-negative (E. coli, K. pneumoniae, and Pseudomonas sp.) bacteria. However, they have not shown inhibition against fungi Aspergillus niger (A. niger), Fusarium oxysporum (F. oxysporum), and C. albicans (C. albicans) [17].

Unfortunately, three new precious neolemnane sesquiterpene lineolemnenes, E, F, G (5–7), and a new aristolane-type sesquiterpenoid, 2-acetoxy-aristolane (8), have tested antibacterial activities against S. aureus and B. cereus with relatively high MIC values [18].

Compound 9, a drimane sesquiterpenoid, exhibited significant antibacterial activity with the MRSA, E. coli, and C. albicans with MIC values of 4, 3, and 8 µg/mL, respectively [19]. Another drimane sesquiterpenoid astellolide Q (10) showed remarkable antifungal activities against Penicillium italicum (P. italicum) and C. gloeosporioides with MIC values both being of 25 µg/mL [20].

Byssocarotins A–D (11–14) displayed antagonism against the marine-derived bacteria Vibrio parahaemolyticus (V. parahaemolyticus) and V. harveyi with MIC values ranging from 13 to 50 µg/mL [21]. Alcyopterosin T (15), Alcyopterosin U (16), and Alcyopterosin V (17) were inactive against the ESKAPE panel of bacterial pathogens. However, compound 17 demonstrated significant efficacy against Clostridium difficile (C. difficile), an intestinal bacterium that is notoriously challenging to treat [22].

Compounds 18–21 exhibited moderate to low antibacterial activity against Bacillus megaterium (B. megaterium) DSM32, with MIC values of 32 µg/mL for each. Furthermore, compounds 19 and 20 inhibited Micrococcus luteus (M. luteus) ATCC 4698 with MIC values of 32 µg/mL [23].

Plakordiols A to D (22–25), (7R, 10R)-hydroxycurcudiol (26), and (7R, 10S)-hydroxycurcudiol (27). None of these compounds, ranging from 22 to 27, exhibited inhibitory effects on a panel of five bacterial strains, including S. aureus ATCC 25923, MRSA ATCC 43300, A. baumannii ATCC 19606, P. aeruginosa (clinical), and VRE CD27. However, compounds 27 and 28 demonstrated weak antibacterial activity against A. baumannii ATCC 19606 in disc diffusion tests, producing inhibition zone diameters of 5 mm each. Despite this, these compounds failed to exhibit significant activity against A. baumannii ATCC 19606 in MIC bioassays, with MIC values exceeding 64 µg/mL [24].

Compounds 28–32 primarily displayed antimicrobial properties against V. harveyi and V. parahaemolyticus, with MIC values varying between 15.0 and 121.2 µg/mL. Notably, antimicrobial assays revealed that compound 29 exhibited superior efficacy to compounds 30 and 31 against the Vibrio species and C. gloeosporioides. These findings suggest hydroxylation at the C-10 or C-11 position may attenuate the antimicrobial activity against these microbial strains [25].

Compound 34 exhibited notable antibacterial potency, demonstrating significant inhibitory effects against S. aureus USA300 LAC, Streptococcus pyogenes (S. pyogenes) ATCC 12344, and Enterococcus faecium (E. faecium) Efm-HS0649. MICs for compound 34 were determined to be 1.5, 1.5, and 3.0 µg/mL for each bacterium, respectively. These MIC values are in the same range as those observed for the positive control, vancomycin, which tested a MIC of 1.0 µg/mL [26].

Remarkably, compound 37 displayed measurable antimicrobial activities when administered 25 mg per disk. This compound exhibited inhibitory effects against a panel of bacterial strains, including Bacillus subtilis (B. subtilis), E. coli, K. pneumoniae, Salmonella typhimurium (S. typhimurium), and S. aureus, with each strain demonstrating an inhibition zone of 3.0 mm in diameter [27]. Malfilanol C (40) exhibited weak antibacterial activity against S. aureus ATCC 29213 [28]. Sesquiterpene glycoside, trichoacorside A (41), demonstrated moderate activity against MRSA and Vibrio harveyi (V. harveyi), an aquatic pathogenic bacterium, with MIC values being 4 µg/mL, the tested plant–pathogenic fungi, including Alternaria brassicae, Calonectria cornigerum, Colletotrichum gloeosporioides with MIC values ranging from 8 to 64 µg/mL [29].

The majority of compounds 42–46, specifically 42–45, demonstrated high MIC values, indicating weak antibacterial potential. In contrast, compound 46 displayed a more pronounced effect, exhibiting moderate antibacterial activity against B. subtilis with an MIC value of 6.25 µg/mL [30]. Both compounds 47 and 48 have shown antibacterial efficacy against P. aeruginosa and Enterococcus faecalis (E. faecalis), with their antibacterial activities quantified in absolute activity units (AUs) [31].

3.2. Diterpenoids

This part elaborates on the antimicrobial effects of 39 diterpenoid substances (compounds 49–87), with additional information found in

Table 6. Antibacterial and/or Antifungal Activities Diterpenoids (49–87).

No.	Test Strains	Activity	Bioassays	Ref.
49	S. aureus	Antibacterial	24% (50 µM), 42% (100 µM), 40% (200 µM) inhibition	[33]
50	S. aureus	Antibacterial	46% (50 µM), 47% (100 µM), 93% (200 µM) inhibition	[33]
51	S. aureus	Inactive	Inactive against S. aureus	[33]
52	V. anguillarum	Antibacterial	MIC = 12.5 µg/mL	[34]
53	V. anguillarum	Inactive	Inactive against V. anguillarum	[34]
54	V. anguillarum	Inactive	Inactive against V. anguillarum	[34]
55	V. anguillarum	Inactive	Inactive against V. anguillarum	[34]
56	V. anguillarum	Inactive	Inactive against V. anguillarum	[34]
57	V. anguillarum	Inactive	Inactive against V. anguillarum	[34]
58	V. anguillarum	Inactive	Inactive against V. anguillarum	[34]
59	V. anguillarum	Antibacterial	MIC = 12.5 µg/mL	[34]
60	V. anguillarum	Inactive	Inactive against V. anguillarum	[34]
61	C. albicans	Antifungal	-	[35]
	E. coli ATCC 11775	Inactive	-
	S. aureus ATCC 25923
	B. subtilis ATCC 6633
62	Exophiala sp. NJM 1551	Antifungal	MIC = 25 µg/mL	[36]
	Fusarium moniliforme NJM 8995		MIC > 100 µg/mL
	F. Oxysporum NJM 0179		MIC = 50 µg/mL
	Fusarium solani NJM 8996		MIC = 50 µg/mL
	Haliphthoros sabahensis IPMB 1402		MIC = 25 µg/mL
	H. Milfordensis IPMB 1603		MIC = 25 µg/mL
	Lagenidium thermophilum IPMB 1401		MIC = 12.5 µg/mL
63	Exophiala sp. NJM 1551	Antifungal	MIC = 50 µg/mL	[36]
	Fusarium moniliforme NJM 8995		MIC > 100 µg/mL
	F. Oxysporum NJM 0179		MIC > 100 µg/mL
	Fusarium solani NJM 8996		MIC > 100 µg/mL
	Haliphthoros sabahensis IPMB 1402		MIC = 25 µg/mL
	H. Milfordensis IPMB 1603		MIC = 50 µg/mL
	Lagenidium thermophilum IPMB 1401		MIC = 25 µg/mL
64	Exophiala sp. NJM 1551	Antifungal	MIC = 50 µg/mL	[36]
	Fusarium moniliforme NJM 8995		MIC > 100 µg/mL
	F. Oxysporum NJM 0179		MIC > 100 µg/mL
	Fusarium solani NJM 8996		MIC > 100 µg/mL
	Haliphthoros sabahensis IPMB 1402		MIC = 50 µg/mL
	H. Milfordensis IPMB 1603		MIC = 50 µg/mL
	Lagenidium thermophilum IPMB 1401		MIC = 25 µg/mL
65	S. aureus	Antibacterial	0 (12.5 µM), 19.1% (100 µM) inhibition	[37]
66	S. aureus	Antibacterial	15.3% (12.5 µM), 29.3% (100 µM) inhibition	[37]
67	S. aureus ATCC 29213	Antibacterial	MIC = 16 µg/mL	[38]
	S. aureus USA300LAC		MIC = 16 µg/mL
	S. Pneumoniae ATCC 49619		MIC = 16 µg/mL
	S. Pneumoniae 549 CHUAC		MIC = 32 µg/mL
	E. Faecalis ATCC 29212		MIC = 32 µg/mL
	E. Faecalis 256 CHUAC		MIC > 64 µg/mL
	E. Faecium 214 CHUAC		MIC = 32 µg/mL
68	S. aureus ATCC 29213	Antibacterial	MIC = 1 µg/mL	[38]
	S. aureus USA300LAC		MIC = 2 µg/mL
	S. Pneumoniae ATCC 49619		MIC = 4 µg/mL
	S. Pneumoniae 549 CHUAC		MIC = 8 µg/mL
	E. Faecalis ATCC 29212		MIC = 4 µg/mL
	E. Faecalis 256 CHUAC		MIC = 4 µg/mL
	E. Faecium 214 CHUAC		MIC = 4 µg/mL
69	S. aureus ATCC 29213	Antibacterial	MIC = 8 µg/mL	[38]
	S. aureus USA300LAC		MIC = 8 µg/mL
	S. Pneumoniae ATCC 49619		MIC = 16 µg/mL
	S. Pneumoniae 549 CHUAC		MIC > 64 µg/mL
	E. Faecalis ATCC 29212		MIC = 16 µg/mL
	E. Faecalis 256 CHUAC		MIC = 32 µg/mL
	E. Faecium 214 CHUAC		MIC = 8 µg/mL
70	S. aureus	Antibacterial	MIC = 8 µg/mL	[39]
	B. subtilis		MIC = 4 µg/mL
71	S. aureus	Antibacterial	MIC = 8 µg/mL	[39]
	B. subtilis		MIC = 4 µg/mL
72	S. aureus	Inactive	MIC > 128 µg/mL	[39]
	B. subtilis		MIC = 64 µg/mL
73	S. aureus	Inactive	MIC > 128 µg/mL	[39]
	B. subtilis		MIC = 64 µg/mL
74	S. aureus	Inactive	MIC > 128 µg/mL	[39]
	B. subtilis
75	S. aureus	Inactive	MIC > 128 µg/mL	[39]
	B. subtilis		MIC = 64 µg/mL
76	S. aureus	Antibacterial	MIC = 32 µg/mL	[40]
	B. subtilis		MIC = 32 µg/mL
	V. harveyi		MIC = 64 µg/mL
	S. Pneumoniae		MIC > 128 µg/mL
	E. coli		MIC > 128 µg/mL
77	S. aureus	Antibacterial	MIC = 32 µg/mL	[40]
	B. subtilis		MIC = 32 µg/mL
	V. harveyi		MIC = 64 µg/mL
	S. Pneumoniae		MIC > 128 µg/mL
	E. coli		MIC > 128 µg/mL
78	S. aureus	Antibacterial	MIC = 64 µg/mL	[40]
	B. subtilis		MIC = 32 µg/mL
	V. harveyi		MIC > 128 µg/mL
	S. Pneumoniae		MIC > 128 µg/mL
	E. coli		MIC > 128 µg/mL
79	S. aureus	Antibacterial	MIC = 64 µg/mL	[40]
	B. subtilis		MIC = 64 µg/mL
	V. harveyi		MIC > 128 µg/mL
	S. Pneumoniae		MIC > 128 µg/mL
	E. coli		MIC > 128 µg/mL
80	S. aureus	Antibacterial	MIC = 64 µg/mL	[40]
	B. subtilis		MIC = 32 µg/mL
	V. harveyi		MIC > 128 µg/mL
	S. Pneumoniae		MIC > 128 µg/mL
	E. coli		MIC > 128 µg/mL
81	S. aureus	Antibacterial	MIC = 16 µg/mL	[40]
	B. subtilis		MIC = 16 µg/mL
	V. harveyi		MIC > 128 µg/mL
	S. Pneumoniae		MIC > 128 µg/mL
	E. coli		MIC = 8 µg/mL
82	S. aureus	Antibacterial	MIC = 32 µg/mL	[40]
	B. subtilis		MIC = 16 µg/mL
	V. harveyi		MIC = 64 µg/mL
	S. Pneumoniae		MIC > 128 µg/mL
	E. coli		MIC = 32 µg/mL
83	S. aureus	Antibacterial	MIC = 8 µg/mL	[18]
	B. Cereus
84	S. aureus	Antibacterial	MIC = 4 µg/mL	[18]
	B. Cereus		MIC = 16 µg/mL
85	S. aureus	Antibacterial	MIC = 4 µg/mL	[18]
	B. Cereus		MIC = 16 µg/mL
86	S. aureus	Antibacterial	MIC = 16 µg/mL	[18]
	B. Cereus		MIC = 8 µg/mL
87	S. aureus	Antibacterial	MIC = 16 µg/mL	[18]
	B. Cereus		MIC = 8 µg/mL

“-” indicates that the MIC value is beyond the detectable range.

.

Three novel 5,5,6,6,5-pentacyclic spongian diterpenes, numbered 49–51, have been isolated. Subsequent in vitro assays were conducted to evaluate their growth inhibitory effects on S. aureus. Notably, spongenolactone A (49) demonstrated significant inhibitory activity, achieving 46%, 47%, and 93% growth inhibition at concentrations of 50, 100, and 200 µM, respectively. In contrast, spongenolactone B (50) showed comparatively lower inhibitory effects, with 24%, 42%, and 40% growth inhibition observed at the same concentration gradients [33].

Compounds 52–60 have exhibited various biological activities, including anti-influenza A virus, protein tyrosine phosphatase inhibitory effects, and anti-Vibrio properties. In particular, their potential to resist Vibrio species has attracted significant interest. Notably, compounds 52 and 59 have demonstrated weak anti-Vibrio activity against Vibrio anguillarum (V. anguillarum), with MICs of 12.5 and 25.0 µg/mL, respectively [34].

Noonidole A (61) exhibited moderate antifungal activity. Regrettably, it did not demonstrate antibacterial activity against bacteria, including E. coli ATCC 11775, S. aureus ATCC 25923, and B. subtilis ATCC 6633 [35].

Compound 62 displayed significant antifungal activity, with a MIC value of 12.5 µg/mL against the hyphal growth inhibition of Lentinula thermophilum. SAR analysis revealed that the differential antifungal potency between compounds 62 and 63 may be ascribed to the presence of an epoxide ring in compound 63. Furthermore, the trisubstitution of methyl groups in the β-configuration within compound 63 could introduce steric hindrance compared to compound 62, potentially impacting its antifungal efficacy [36].

Compound 65 demonstrated a concentration-dependent inhibitory effect on the growth of S. aureus, with inhibition rates of 15.3% and 29.3% at concentrations of 12.5 µM and 100 µM, respectively. Additionally, compound 65 effectively reduced biofilm formation by S. aureus, with prevention rates of 15.9% and 34.5% at the same concentrations. Conversely, compound 66 showed a weaker effect on S. aureus growth, with inhibition of 19.1% at 100 µM and no significant impact at 12.5 µM. However, it notably inhibited biofilm formation, with prevention rates ranging from 37.9% at 12.5 µM to 52.6% at 100 µM. The half-maximal inhibitory concentration (IC₅₀) for the inhibition of S. aureus biofilm formation by compound 66 was determined to be 76.1 µM [37]

(+)-8-epiagelasine T (67), (+)-10-epiagelasine B (68), and (+)-12-hydroxyagelasidine C (70) did not exhibit activity against the Gram-negative pathogens A. baumannii ATCC 17978, K. pneumoniae ATCC 700603, and P. aeruginosa ATCC 27823. However, these compounds did demonstrate antibacterial activity against a range of Gram-positive pathogens. This group included S. aureus ATCC 29213, S. aureus USA300LAC, Streptococcus pneumoniae (S. pneumoniae) ATCC 49619, S. pneumoniae 549 CHUAC, E. faecalis ATCC 29212, E. faecalis 256 CHUAC and E. faecium 214 CHUAC [38].

Lemnaboursides E-G (70–72) and lemnadiolboursides A–C (73–75) demonstrated discernible antibacterial activity, targeting both S. aureus and B. subtilis with MIC values ranging from 4 to 16 µg/mL. A comprehensive assessment integrating antimicrobial assays with detailed structural analyses has indicated a potential correlation between the steric hindrance of the glycosides and their antimicrobial efficacy, particularly with respect to the lemnaboursides [39].

The antibacterial activities of compounds 76–82 were systematically evaluated against a panel of five pathogenic bacteria, including S. aureus, B. subtilis, V. harveyi, S. pneumoniae, and E. coli. Notably, all compounds within the series (76–82) demonstrated antibacterial efficacy against S. aureus and B. subtilis, with MICs varying from 4 to 64 µg/mL [40]. Compounds 83–87 exhibited antimicrobial properties, demonstrating antibacterial activity against S. aureus and B. cereus with MICs ranging from 4 to 16 µg/mL [18].

3.3. Triterpenoids

This section offers a comprehensive examination of the antimicrobial properties of 20 triterpenoid compounds, numbered 88 to 107, with further details available in

Table 7. Antibacterial and/or Antifungal Activities Triterpenoids (88–105).

No.	Test Strains	Activity	Bioassays	Ref.
88	S. aureus USA300LAC	Antibacterial	MIC = 28.1 µg/mL	[41]
	S. pyogenes ATCC12344		MIC = 1.8 µg/mL
89	S. aureus USA300LAC	Antibacterial	MIC = 30.9 µg/mL	[41]
	S. pyogenes ATCC12344		MIC = 1.0 µg/mL
90	S. aureus USA300LAC	Antibacterial	MIC > 250.0 µg/mL	[41]
	S. pyogenes ATCC12344		MIC = 120.0 µg/mL
91	S. aureus USA300LAC	Antibacterial	MIC > 250.0 µg/mL	[41]
	S. pyogenes ATCC12344
92	S. aureus USA300LAC	Antibacterial	MIC > 250.0 µg/mL	[41]
	S. pyogenes ATCC12344		MIC = 65.9 µg/mL
93	S. aureus USA300LAC	Antibacterial	MIC > 250.0 µg/mL	[41]
	S. pyogenes ATCC12344		MIC = 124.5 µg/mL
94	S. aureus USA300LAC	Antibacterial	MIC > 250.0 µg/mL	[41]
	S. pyogenes ATCC12344
95	S. aureus USA300LAC	Antibacterial	MIC > 250.0 µg/mL	[41]
	S. pyogenes ATCC12344
96	S. aureus USA300LAC	Antibacterial	MIC > 250.0 µg/mL	[41]
	S. pyogenes ATCC12344		MIC = 240.0 µg/mL
98	S. aureus	Antibacterial	MIC > 100 µg/mL	[42]
100	S. aureus	Antibacterial	MIC > 100 µg/mL	[42]
101	S. aureus	Antibacterial	MIC > 100 µg/mL	[42]
102	S. aureus	Antibacterial	MIC > 100 µg/mL	[42]
104	S. aureus	Antibacterial	MIC = 2.5 µg/mL	[42]
105	S. aureus	Antibacterial	MIC = 0.078 µg/mL	[42]

.

Nine novel isomalabaricane terpenoids, numbered 88–96, were tested against S. aureus USA300LAC and S. pyogenes ATCC12344. In this series, compounds 89 and 90 showed a substantial antibacterial effect against S. pyogenes, with MIC values recorded at 1.8 and 1.0 µg/mL, respectively [41].

Compound 105 exhibited potent antibacterial activity against S. aureus, with a remarkably low MIC value of 0.078 µg/mL. A subset of the compounds, specifically 98, 100–102, 104, and 105, were selected for their targeted evaluation of antibacterial activity against S. aureus. However, compounds 97, 99, 103, 106, and 107 were excluded from the antibacterial panel due to their limited availability and the susceptibility of compound 97 to hydrolysis. Drawing on previous SAR studies, the chemical structure of fusidic acid has been established as optimal for antibacterial potency, with the C-21 carboxylic acid group being an essential moiety for activity [54]. The antibacterial findings for compounds 98, 100, 101, 102, 104, and 105 corroborated this established conclusion. Furthermore, a comparative analysis of the structures and antibacterial profiles of compounds 104, 105, and fusidic acid indicated that the oxidation of the C-11 position to a carbonyl group did not significantly impact antibacterial efficacy. In contrast, the oxidation of the hydrophobic side chain at the C-20 position was associated with decreased antibacterial activity [42].

3.4. Meroterpenoids

This section details the antimicrobial properties of meroterpenoid compounds 108–141, with details in

Table 8. Antibacterial and/or antifungal activities meroterpenoids (108–141).

No.	Test Strains	Activity	Bioassays	Ref.
108	A. hydrophilia	Antibacterial	MIC = 32 µg/mL	[46]
	E. coli		MIC = 16 µg/mL
	E. Tarda		MIC = 0.5 µg/mL
	V. anguillarum		MIC = 0.5 µg/mL
	V. harveyi		MIC = 32 µg/mL
	C. Diplodiella,	Antifungal	MIC = 8 µg/mL
	F. Graminearum		MIC = 32 µg/mL
109	A. hydrophilia	Antibacterial	MIC = 16 µg/mL
	E. coli		MIC = 1 µg/mL	[46]
	E. Tarda		MIC = 32 µg/mL
	V. anguillarum		MIC = 4 µg/mL
	V. harveyi		MIC = 32 µg/mL
	C. Diplodiella	Antifungal	MIC = 64 µg/mL
	F. Graminearum
110	A. hydrophilia	Antibacterial	MIC = 32 µg/mL	[46]
	E. coli		MIC = 32 µg/mL
	E. Tarda		MIC = 16 µg/mL
	V. anguillarum		MIC = 32 µg/mL
	V. harveyi		MIC = 16 µg/mL
	C. Diplodiella	Antifungal	MIC > 64 µg/mL
	F. Graminearum		MIC > 32 µg/mL
111	A. hydrophilia	Antibacterial	MIC = 32 µg/mL	[46]
	E. coli		MIC = 16 µg/mL
	E. Tarda		MIC = 0.5 µg/mL
	V. anguillarum		MIC = 0.5 µg/mL
	V. harveyi		MIC = 32 µg/mL
	C. Diplodiella	Antifungal	MIC = 8 µg/mL
	F. Graminearum		MIC = 32 µg/mL
112	S. aureus ATCC6538P	Antibacterial	MIC = 15.2 µg/mL	[47]
	E. coli		-
	V. Parahaemolyticus	Antifungal	-
116	S. aureus CICC 10384	Antibacterial	MIC = 12.5 µg/mL	[48]
119	M. lutea	Antibacterial	MIC = 6.25 µg/mL	[49]
	K. Pneumoniae		MIC = 50 µg/mL
	MRSA		MIC = 6.25 µg/mL
	S. faecalis		MIC = 6.25 µg/mL
120	M. lutea	Antibacterial	MIC = 25 µg/mL	[49]
	K. Pneumoniae		MIC > 100 µg/mL
	MRSA		MIC = 6.25 µg/mL
	S. faecalis		MIC = 25 µg/mL
121	M. lutea	Antibacterial	MIC = 25 µg/mL	[49]
	K. Pneumoniae		MIC = 25 µg/mL
	MRSA		MIC = 12.5 µg/mL
	S. faecalis		MIC > 100 µg/mL
122	M. lutea	Antibacterial	MIC > 100 µg/mL	[49]
	K. Pneumoniae		MIC = 6.25 µg/mL
	MRSA		MIC = 25 µg/mL
	S. faecalis		MIC = 50 µg/mL
123	M. lutea	Antibacterial	MIC = 12.5 µg/mL	[49]
	K. Pneumoniae		MIC > 100 µg/mL
	MRSA		MIC = 12.5 µg/mL
	S. faecalis		MIC = 12.5 µg/mL
124	M. lutea	Inactive	MIC > 100 µg/mL	[49]
	K. Pneumoniae
	MRSA
	S. faecalis
125	S. aureus ATCC6538	Antibacterial	MIC > 128 µg/mL	[50]
	B. subtilis ATCC 6633
	E. coli ATCC 25922
	L. Monocytogenes ATCC 1911
	F. Oxysporum f. Sp. Cubense	Inactive	MIC > 128 µg/mL
	Fusarium spp.
	P. Litchii
	C. Gloeosporioides
	H. Undatus
126	S. aureus ATCC6538	Antibacterial	MIC > 128 µg/mL	[50]
	B. subtilis ATCC 6633
	E. coli ATCC 25922
	L. Monocytogenes ATCC 1911
	F. Oxysporum f. Sp. Cubense	Inactive	MIC > 128 µg/mL
	Fusarium spp.
	P. Litchii
	C. Gloeosporioides
	H. Undatus
127	S. aureus ATCC6538	Antibacterial	MIC > 128 µg/mL	[50]
	B. subtilis ATCC 6633
	E. coli ATCC 25922
	L. Monocytogenes ATCC 1911
	F. Oxysporum f. Sp. Cubense	Inactive	MIC > 128 µg/mL
	Fusarium spp.
	P. Litchii
	C. Gloeosporioides
	H. Undatus
128	S. aureus ATCC6538	Antibacterial	MIC > 128 µg/mL	[50]
	B. subtilis ATCC 6633
	E. coli ATCC 25922
	L. Monocytogenes ATCC 1911
	F. Oxysporum f. Sp. Cubense	Inactive	MIC > 128 µg/mL
	Fusarium spp.
	P. Litchii
	C. Gloeosporioides
	H. Undatus
129	S. aureus ATCC6538	Antibacterial	MIC = 128 µg/mL	[50]
	B. subtilis ATCC 6633		MIC > 128 µg/mL
	E. coli ATCC 25922		MIC > 128 µg/mL
	L. Monocytogenes ATCC 1911		MIC > 128 µg/mL
	F. Oxysporum f. Sp. Cubense	Inactive	Inactive against F. Oxysporum f. Sp. Cubense
	Fusarium spp.		Inactive against Fusarium spp.
	P. Litchii		Inactive against P. Litchii
	C. Gloeosporioides		Inactive against C. Gloeosporioides
	H. Undatus		Inactive against H. Undatus
130	S. aureus ATCC6538	Antibacterial	MIC > 128 µg/mL	[50]
	B. subtilis ATCC 6633
	E. coli ATCC 25922
	L. Monocytogenes ATCC 1911
	F. Oxysporum f. Sp. Cubense	Inactive	MIC > 128 µg/mL
	Fusarium spp.
	P. Litchii
	C. Gloeosporioides
	H. Undatus
131	S. aureus ATCC6538	Antibacterial	MIC > 128 µg/mL	[50]
	B. subtilis ATCC 6633
	E. coli ATCC 25922
	L. Monocytogenes ATCC 1911
	F. Oxysporum f. Sp. Cubense	Inactive	MIC > 128 µg/mL
	Fusarium spp.
	P. Litchii
	C. Gloeosporioides
	H. Undatus
132	S. aureus ATCC6538	Antibacterial	MIC > 128 µg/mL	[50]
	B. subtilis ATCC 6633
	E. coli ATCC 25922
	L. Monocytogenes ATCC 1911
	F. Oxysporum f. Sp. Cubense	Inactive	MIC > 128 µg/mL
	Fusarium spp.
	P. Litchii
	C. Gloeosporioides
	H. Undatus
133	MRSA	Antibacterial	MIC = 25 µg/mL	[20]
	B. subtilis		MIC = 6.25 µg/mL
	P. Aeruginosa		MIC > 50 µg/mL
	S. Typhimurium		MIC > 50 µg/mL
	P. Italicum	Antifungal	MIC = 6.25 µg/mL
	C. Gloeosporioides
134	MRSA	Antibacterial	MIC = 25 µg/mL	[20]
	B. subtilis		MIC = 25 µg/mL
	P. Aeruginosa		MIC = 25 µg/mL
	S. Typhimurium		MIC > 50 µg/mL
	P. Italicum	Antifungal	MIC = 50 µg/mL
	C. Gloeosporioides		MIC > 50 µg/mL
135	MRSA	Antibacterial	MIC > 50 µg/mL	[20]
	B. subtilis
	P. Aeruginosa
	S. Typhimurium
	P. Italicum	Antifungal	MIC = 50 µg/mL
	C. Gloeosporioides		MIC > 50 µg/mL
136	B. subtilis KCTC 1021	Antibacterial	MIC = 16 µg/mL	[51]
	K. Rhizophila KCTC 1915		MIC = 32 µg/mL
	S. aureus KCTC 1927		MIC = 16 µg/mL
	E. coli KCTC 2441		MIC > 128 µg/mL
	S. Typhimurium KCTC 2515		MIC > 128 µg/mL
	K. Pneumonia KCTC 2690		MIC > 128 µg/mL
137	B. subtilis KCTC 1021	Antibacterial	MIC = 64 µg/mL	[51]
	K. Rhizophila KCTC 1915		MIC > 128 µg/mL
	S. aureus KCTC 1927		MIC > 128 µg/mL
	E. coli KCTC 2441		MIC > 128 µg/mL
	S. Typhimurium KCTC 2515		MIC > 128 µg/mL
	K. Pneumonia KCTC 2690		MIC > 128 µg/mL
138	B. subtilis KCTC 1021	Antibacterial	MIC = 1 µg/mL	[51]
	K. Rhizophila KCTC 1915		MIC = 2 µg/mL
	S. aureus KCTC 1927		MIC = 2 µg/mL
	E. coli KCTC 2441		MIC > 128 µg/mL
	S. Typhimurium KCTC 2515		MIC > 128 µg/mL
	K. Pneumonia KCTC 2690		MIC > 128 µg/mL
139	B. subtilis KCTC 1021	Antibacterial	MIC > 128 µg/mL	[51]
	K. Rhizophila KCTC 1915
	S. aureus KCTC 1927
	E. coli KCTC 2441
	S. Typhimurium KCTC 2515
	K. Pneumonia KCTC 2690
140	H. pylori ATCC43504	Antibacterial	MIC = 2 µg/mL	[52]
	H. pylori G27		MIC = 1 µg/mL
	H. pylori Hp159		MIC = 1 µg/mL
	H. pylori BY583		MIC = 4 µg/mL
	S. aureus ATCC25923		MIC = 16 µg/mL
	S. aureus USA300		MIC = 2 µg/mL
	S. aureus BKS231		MIC = 4 µg/mL
	S. aureus BKS233		MIC = 8 µg/mL
141	E. coli	Antibacterial	MIC = 8 µg/mL	[53]
	M. Luteus		MIC = 8 µg/mL
	P. Aeruginosa		MIC = 16 µg/mL
	R. Solanacearum		MIC = 8 µg/mL
	A. Alternata	Antifungal	MIC > 64 µg/mL
	B. Cinerea		MIC = 32 µg/mL
	F. Oxysporum		MIC > 64 µg/mL
	P. Digitatum		MIC = 32 µg/mL
	V. Mali		MIC = 16 µg/mL

“-” indicates that the MIC value is beyond the detectable range.

.

Chermesins E–H (108–111) were subjected to a battery of assays to evaluate their antibacterial and antifungal activities against a spectrum of human and aquatic bacteria, including Aeromonas hydrophilia (A. hydrophilia), E. coli, Edwardsiella tarda (E. tarda), V. anguillarum, and V. harveyi, as well as against plant–pathogenic fungi, such as Coniothyrium diplodiella (C. diplodiella), and Fusarium graminearum (F. graminearum). Compound 108 displayed potent antibacterial activity against E. tarda and V. anguillarum, with MICs of 0.5 µg/mL, a value comparable to or exceeding the efficacy of the positive control, chloramphenicol, which showed MICs of 0.5 and 1 µg/mL, respectively. Additionally, compound 110 exhibited robust activity against the human pathogenic bacterium E. coli, with an MIC of 1 µg/mL, surpassing the activity of the positive control, chloromycetin, which had an MIC of 2 µg/mL [46].

Compound 112 exhibited selective antibacterial activity targeting S. aureus ATCC 6538P, demonstrating a noteworthy potency with a MIC of 15.2 µg/mL. This potency, however, was lower than that of the positive control, chloramphenicol, which had an MIC of 5.0 µg/mL. Compound 112’s antibacterial activity was less pronounced against V. parahaemolyticus and E. coli strains [47]. Moving on to compound 116, it also showed selective antibacterial activity against S. aureus CICC 10384, with an MIC of 12.5 µg/mL. This activity was on par with chloramphenicol, again serving as a positive control with an MIC of 5.0 µg/mL [48].

Compounds 119–124 were subjected to a broth dilution assay to evaluate their antibacterial activity against a panel of bacterial strains, including M. luteus, K. pneumoniae, MRSA, and Streptococcus faecalis (S. faecalis). The compounds exhibited a range of antibacterial potencies, with MICs spanning from 6.25 to 100 µg/mL [49].

Compound 129 exhibited modest inhibitory effects against S. aureus with a MIC of 128 µg/mL. Compounds (125–128 and 130–132) demonstrated lackluster antibacterial properties, with MICs exceeding 128 µg/mL for both S. aureus and B. subtilis. Subsequently, the inhibitory activities of the same set of compounds were evaluated against five phytopathogenic fungi, including F. oxysporum f. sp. cubense, Fusarium spp, Peronophythora litchii (P. litchii), C. gloeosporioides, Hylocereus undatus (H. undatus) utilizing the broth microdilution technique. Regrettably, under the conditions tested, none of the compounds manifested definitive inhibitory effects against the tested fungi [50].

Hemiacetalmeroterpenoids A to C (133–135) exhibit more potent antimicrobial activities against phytopathogenic fungi than their effects on bacteria. Specifically, compound 135 displayed significant antimicrobial effects against B. subtilis, P. italicum, and C. gloeosporioides with MIC of 6.25 µg/mL for all three organisms. Furthermore, compound 135 also demonstrated antibacterial activity against MRSA, with an MIC of 25 µg/mL [20].

Compound 138 exhibited robust antibacterial activity against Gram-positive strains: B. subtilis KCTC 1021, K. rhizophila KCTC 1915, and S. aureus KCTC 1927. The MICs for these strains were 1, 2, and 2 µg/mL, respectively. In contrast, compound 139 exhibited no significant antibacterial activity against the same strains, with all MICs greater than 128 µg/mL [51].

Compound 140 has demonstrated potent antimicrobial activity against various strains of Helicobacter pylori (H. pylori), including ATCC43504, G27, Hp159, and BY583, with MICs ranging from 1 to 4 µg/mL. Additionally, aspergillactone (140) exhibited significant inhibitory effects against multiple strains of S. aureus, such as ATCC25923, USA300, BKS231, and BKS233, with MICs in the range of 2 to 16 µg/mL [52].

Compound 141 demonstrated inhibitory effects against E. coli, M. luteus, and Ralstonia solanacearum (R. solanacearum) with MICs consistent at 8 µg/mL. However, against P. aeruginosa, the MIC was found to be higher at 16 µg/mL. In parallel with the antibacterial assessments, the antifungal activity of 141 was also evaluated. The compound exhibited notable antifungal activity against a panel of five plant pathogenic fungi, including Alternaria alternata (A. alternata), Botrytis cinerea (B. cinerea), F. oxysporum, Penicillium digitatum (P. digitatum), and Valsa mali (V. mali). Notably, the most potent activity was observed against V. mali, with an MIC value of 16 µg/mL [53].

4. Conclusions

This review summarizes 141 terpenoid compounds with antibacterial and/or antifungal activities discovered from marine biological resources between 2019 and 2024. These compounds are primarily derived from sponges, red algae, soft corals, fungi, bacteria, and marine sediments. They include 48 sesquiterpenes, 39 diterpenes, 20 triterpenes, and 34 meroterpenoids.

The antibacterial activity of these compounds is relatively evenly distributed and does not show a particular preference for any specific skeletal type. Among sesquiterpenes, compounds such as 9 and 34 exhibit significant antibacterial activity against S. aureus, with MICs ranging from 4 to 1.5 µg/mL. Diterpenes, including compounds 68, 71, 83–87, also show promising antibacterial activity with MICs between 1 and 8 µg/mL. Notably, the fusidane-type nortriterpenoid compound 105 has the lowest MIC at 0.078 µg/mL, demonstrating strong antibacterial activity. Among meroterpenoids, compound 108 has significant antifungal activity against animal pathogens V. anguillarum and V. harveyi, with an MIC as low as 0.5 µg/mL. Compound 123 demonstrated potent antibacterial activity against M. lutea and S. faecalis, with MIC values of 12.5 µg/mL. Compound 140 showed strong antibacterial activity against H. pylori strains ATCC43504, G27, and Hp159, with MIC values as low as 1 µg/mL.

Among the 141 terpenoid compounds surveyed, those with antibacterial activity against S. aureus were most abundant, comprising 40 unique compounds. The count was followed by 21 compounds active against V. harveyi, 18 against B. subtilis, 14 against E. coli, and 10 each with efficacy against MRSA, V. anguillarum, and V. Parahaemolyticus. There were nine compounds with activity against S. pyogenes, eight compounds against B. Cereus, and terpenoid compounds with activity against C. Gloeosporioides, E. Faecium, K. Pneumoniae, A. hydrophilia, and E. Faecalis were five each. There were four compounds each against P. Italicum, P. Aeruginosa, F. Graminearum, and E. Tarda, and three against B. megaterium, M. Luteus, Exophiala sp., Haliphthoros sabahensis, H. Milfordensis, Lagenidium thermophilum, S. pneumoniae, and C. Diplodiella. The number of terpenoid compounds resistant to F.Oxysporum, P.Digitatum, K.Rhizophila, and C. albicans strains was 2, respectively. Notably, compound 17 exhibited antibacterial properties against C. difficile. Among the surveyed terpenoid compounds, compound 41 is the sole terpenoid with demonstrated antibacterial activity against the strains A. Brassicae, C. Cornigerum, Curvularia spicifera, Fusarium proliferatum, and P. Piricola. The sole compound exhibiting antibacterial activity against the A. baumannii strain is compound 27, producing inhibition zone diameters of 5.0 ± 0.6 mm. However, the compound’s MIC exceeds 64 µg/mL. Compound 62 is the only compound that exhibits resistance against the Fusarium solani strain. Compound 140 is the unique compound with antibacterial resistance against H. pylori and has demonstrated strong antibacterial activity against H. pylori strains, with an MIC of 2 µg/mL. Compound 141 stands out as the sole terpenoid to demonstrate resistance against R. solanacearum, with an MIC value of 8 µg/mL.

Furthermore, SAR analysis indicates that hydroxylation at C-10 and C-11 in compounds 29, 30, and 31 may reduce antibacterial activity; the β-configuration of the trimethyl substitution in compound 63 may decrease antifungal efficacy through steric hindrance. The structural analysis of compounds 73–75 suggests that the spatial hindrance of glycosides is related to antimicrobial efficacy.

In conclusion, marine terpenoids have demonstrated considerable potential for development in the antimicrobial domain. This discovery is not only of profound significance to the pharmaceutical industry in the quest for novel antimicrobial agents but also holds promise for its potential applications in various fields, including animal nutrition and food preservation.