Next Article in Journal
Description and Genomic Characterization of Oceaniferula flavus sp. nov., a Novel Potential Polysaccharide-Degrading Candidate of the Difficult-to-Cultivate Phylum Verrucomicrobiota Isolated from Seaweed
Next Article in Special Issue
Marine Sponge and Octocoral-Associated Bacteria Show Versatile Secondary Metabolite Biosynthesis Potential and Antimicrobial Activities against Human Pathogens
Previous Article in Journal
Diversity of Bacterial Secondary Metabolite Biosynthetic Gene Clusters in Three Vietnamese Sponges
Previous Article in Special Issue
Antimicrobial Biosynthetic Potential and Phylogenetic Analysis of Culturable Bacteria Associated with the Sponge Ophlitaspongia sp. from the Yellow Sea, China
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Marine Drugs
Volume 21
Issue 1
10.3390/md21010030
marinedrugs-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

The Soft Coral Sarcophyton trocheliophorum: A Warehouse of Terpenoids with Structural and Pharmacological Diversity

by
Qi-Bin Yang
1,
Qihao Wu
2,3,
Jun-Kun Chen
1 and
Lin-Fu Liang
1,*
1
College of Materials Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China
2
Department of Chemistry, Yale University, New Haven, CT 06520, USA
3
Institute of Biomolecular Design & Discovery, Yale University, West Haven, CT 06516, USA
*
Author to whom correspondence should be addressed.
Mar. Drugs 2023, 21(1), 30; https://doi.org/10.3390/md21010030
Submission received: 28 November 2022 / Revised: 26 December 2022 / Accepted: 26 December 2022 / Published: 29 December 2022
(This article belongs to the Special Issue Reef Ecology and Marine Drug Discovery)
Browse Figures
Versions Notes

Abstract

:
The soft coral Sarcophyton trocheliophorum, which was frequently encountered on Indo-Pacific and Red Sea coral reefs, furnished a wealth of secondary metabolites. Notably, terpenoids dominated the chemical profile of this species. In this review, we summarized the discovery of 156 terpenoids from the soft coral S. trocheliophorum specimens in different geographical areas. The structures comprised 13 terpenoidal classes with various functionalities. We covered the era from the first report of S. trocheliophorum-derived metabolites in 1976 up to October 2022. The biological effects of these chemical compositions on a vast array of potential pharmacological activities such as protein tyrosine phosphatase 1B (PTP1B) inhibitory, neuroprotective, cytotoxic, anti-inflammatory, antibacterial, antivirus, and immunomodulatory activities were also presented. This review also revealed an immense demand to explore the terpene biosynthetic gene clusters of this species besides the chemo- and bio-investigations.

1. Introduction

Taxonomically, the soft coral species Sarcophyton trocheliophorum belongs to the genus Sarcophyton in the family Alcyoniidae (phylum, Cnidaria; class, Anthozoa; subclass, Octocorallia; order, Alcyonaceae) [1,2]. This benthic soft coral has been frequently encountered on the coral reefs in the Indo-Pacific region, including the South China Sea, Red Sea, and the waters of Okinawa, Indonesia, and Australia [1,2]. Notably, this species has captured the extensive attention of worldwide scientists from China, Australia, India, Saudi Arabia, Egypt, etc., with studies on its chemical composition. Since the first chemical investigation reported in 1976 [3], continuous chemical studies on this soft coral have led to the discovery of numerous secondary metabolites with diverse structural features, implying that S. trocheliophorum has become one of the hotspots of marine natural product research. Structurally, these chemical compositions comprise terpenes [4,5,6,7], steroids [8,9,10,11], prostaglandins [12], γ-butenolides [12,13], phenolics [14], etc. Among these metabolites, terpenoids are the dominative constituents. Up to October 2022, 156 terpenoids with various bioactivities have been identified from the soft coral S. trocheliophorum.
In order to better understand the medicinal significance of terpenoids from soft coral S. trocheliophorum, this review provides the first comprehensive overview of the chemical and/or biological investigations of this soft coral. It covers topics ranging from the distribution of S. trocheliophorum to the compound isolation and structural elucidation together with bioactivity evaluation of different types of terpenoids, within a literature survey since its first discovery in 1976 to October 2022.

2. Overview of Terpenoids from S. trocheliophorum

As revealed in the literature [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51], most of the chemically investigated S. trocheliophorum specimens were collected off the islands in the South China Sea and Indian Ocean, and off the coasts of Saudi Arabia, Egypt, and Australia. These collection sites can be divided into three sea waters: the Pacific Ocean, the Indian Ocean, and the Red Sea. Most of the specimens originated from the Pacific Ocean (Table S1) [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. In this review, terpenoids from S. trocheliophorum were classified into three classes: sesquiterpenoids, diterpenoids, and biscembranoids. Among them, diterpenoids were the most common terpenoids from this species, accounting for 89.1% of all descriptions in the literature (Table S1) [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. These three terpenoid classes were further categorized based on their different skeletal types: trocheliophorane, aromadendrane, elemane, caryophillane, and bisabolane for sesquiterpenoids; cembrane, perhydrophenanthrane, capnosan, sarsolenane, and sarcotroane for diterpenoids; bissartrane, trocheliane, and glaucumane for biscembranoids (Figure 1). Notably, these terpenoids exhibited a broad spectrum of biological activities, such as protein tyrosine phosphatase 1B (PTP1B) inhibitory, neuroprotective, cytotoxic, anti-inflammatory, antibacterial, antivirus, and immunomodulatory activities [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. As shown in Figure 2, the majority of terpenoids were screened for cytotoxic (including antitumor), antibacterial and PTP1B inhibitory activities [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51].

3. Sesquiterpenoids

Sesquiterpenoids were rarely found in S. trocheliophorum. Only six sesquiterpenoids with five different carbon skeletons have been reported (Figure 3). The chemical investigation on the soft coral S. trocheliophorum collected from Kurside Island, Indian Ocean, led to the isolation and identification of trocheliophorin (1), the first report of sesquiterpenoid from this species [15]. Metabolite 1 was a novel rearranged sesquiterpenoid with an aromatic ring; however, its formation has not been explained on the basis of sequiterpenoid biogenetic considerations. As reported, it could be considered as a degradative product of a diterpenoid. The specimen collected off the Saudi Arabia Red Sea coast at Jeddah afforded an aromadendrane sesquiterpenoid palustrol (2) [16]. This tricyclic sesquiterpenoid 2 possessed a broad spectrum of biological activities including antibacterial, antifungal, antifeedant, and antitumor effects. The antimicrobial bioassay revealed that 2 showed moderate activities against Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus aureus MRSA, Micrococcus spp., Streptococcus pneumonia, Acnietobacter spp., Klebsiella pneumonia, Pseudomonas aeruginosa, and Escherichia coli with diameters of inhibition zones ranging from 8 to 11 mm. Meanwhile, 2 had moderate antifungal activities against Candida albicans, Candida tropicals, Aspergillus flavus, and Aspergillus niger (the diameters of inhibition zones were 8–12 mm). Up to 11.1 μM, no toxicity was recorded against Artimia salina as a tested organism for 2. Additionally, 2 showed antitumor activities with LD50 of 2.8 and 3.1 μM for the two tested lymphoma and Erlish cell lines. Another related aromadendrane sesquiterpenoid alloaromadendrene (3) together with β-elemene (4), trans-caryophyllene (5), and bisabolene (6) were isolated from the specimen collected off the east Egypt Red Sea coast at Hurgada [17].

4. Diterpenoids

Diterpenoids are the most abundant secondary metabolites in S. trocheliophorum [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. They showed a variety of biological activities including antitumor, anti-inflammatory, antibacterial, and antifeedant effects [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. The broad bioactivities implied that these secondary metabolites might play important ecological functions in corals’ lives such as antifeedant defenses. At present, diterpenoids from S. trocheliophorum can be categorized into five carbo-skeleton types: cembrane, perhydrophenanthrane, capnosane, sarsolenane, and sarcotroane [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. As indicated in Figure 4, the majority of the diterpenoids were cembrane diterpenoids.

4.1. Cembrane Diterpenoids

The worldwide investigations of soft coral S. trocheliophorum yielded a whole variety of cembranoids with different degrees of oxidation. One or more of the methyl groups were oxidized to a hydroxymethyl group or a carboxyl group. These groups usually appeared as methyl esters, five- to seven-membered oxacycles, and lactone moieties. Herein, this review encompasses the different categories of cembrane diterpenoids as follows: isopropyl/isopropenyl, furane, pyrane, γ-lactone, ε-lactone, and other miscellaneous.

4.1.1. Isopropyl/Isopropenyl Cembranoids

At present, 48 isopropyl/isopropenyl cembranoids from the soft coral S. trocheliophorum distributed in different geographical locations have been disclosed (Figure 5).
In the first chemical study of S. trocheliophorum in 1976 by Tursch, an isopropyl cembrane diterpenoid trocheliophorol (7) was discovered from the soft coral collected in the Seychelles Islands [3]. At first, only the absolute configuration of C-1 was determined to be 1S [18]. Later, the absolute configurations of C-4, C-11, and C-12 were elucidated as 4R,11S,12S by Kashman et al. [19] and Coll et al. [20], respectively. In addition, trocheliophorol (7), thunbergol (8), and 7,8-epoxy-1E,3E,11E-cembratriene-15-ol (9) were found in the sample collected on Orpheus Island [20]. These isolates played a defensive role against the sea slug predator Phyllodesmium longicirra.
In 1985, Elyakov and co-workers reported two related isopropenyl cembrane diterpenoids 13S-hydroxy-(-)-neocembrene (10) and 13S-hydroxy-11,12-epoxy-(-)-neocembrene (11) from another collection of this soft coral on the reefs of the Seychelle Islands [21]. The X-ray diffraction analysis of the well-crystallized p-nitrobenzoate of 8 together with the successful application of Horeau’s method established the 13S absolute configuration for 10. Epoxidation of the alcohol 10 yielded epoxyalcohol 11, revealing the 11S,12S absolute configurations for 11. In Elyakov’s further study on this specimen, the existence of neocembrene (12) was confirmed [22]. The cytostatic activities of compounds 10–12 were determined using a radiometric method in a micro-modification from the level of inclusion of [3H]thymidine, [14C]uridine, and [3H]leucine in the acid-insoluble fraction of Ehrlich cells. The results showed that 10 and 11 caused 50% inhibition of the incorporation of [3H]thymidine, [14C]uridine, and [3H]leucine at concentrations of 19.5–49.0 μg/mL, of which 10 displayed higher cytostatic activity. Compound 12 exhibited no cytostatic activity at concentrations of up to 50 μg/mL. This result revealed that the hydroxyl group substituted at C-13 exhibited strong impacts on the cytostatic activity based on the comparison of these three isopropenyl cembranoids. The permeability of the liposomes study showed that diterpene 10 was the most effective inductor of the release of [1-14C]-glucose from the liposomes.
An investigation of metabolites from the soft coral S. trocheliophorum, collected on Orpheus Island, yielded (7R,8R,14S,1E,3E,11E)-7,8-epoxycembra-l,3,11-trien-14-ol (13), (7R,8R,l4S,lE,3E,11E)-14-acetoxy-7,8-epoxycembra-l,3,11-triene (14), and (7R,14S,1E,3E,8E,11E)-cembra-1,3,8,11-tetraene-7,14-diol (15), whose absolute configurations were determined using Mosher’s method [23]. Both 13 and 14 showed similar cytotoxic profiles with IC50 values of 2.5 μg/mL against murine leukemia P388, 5 μg/mL against human lung carcinoma A549, 10 μg/mL against human colon carcinoma HT29, and 10 μg/mL against human melanoma MEL28 cell lines. An examination of a Singaporean specimen resulted 7,8-epoxy-1E,3E,11E-cembratriene-15-ol (9), isoneocembrene (16), and 7,8-epoxy-1E,3E,11E-cembratriene (17) [8]. In the bioassay, cembratertraene 16 showed moderate growth inhibitory activity against human HL60 leukemia, M14 skin melanoma, and MCF7 breast carcinoma cells with EC50 values of 37.2, 74.6, and 72.8 μg/mL, respectively. Both cembratrienes 9 and 17 exhibited a moderate inhibitory effect on the HL60 cell (EC50 = 34.2 and 63.8 μg/mL, respectively), whereas only 9 displayed moderate inhibitory activity against the MCF7 cell with an EC50 value of 54.6 μg/mL.
Two new secondary metabolites, yalongenes A (18) and B (19), were isolated from the South China Sea soft coral S. trocheliophorum collected in Yalong Bay, Hainan Island [24]. Compounds 18 and 19 were tested for their cytoprotective effects on SH-SY5Y cell injury induced by hydrogen peroxide, and the results showed that compound 19 had significant cytoprotective activity at the concentration of 1.0 μM. It appeared that the Z-configuration of the conjugated olefinic bond Δ3 played a key role for the cytoprotective activity of isopropenyl cembranoids due to the observation of considerable activity for 19 and no activity for 18. From another collection of this soft coral on the reefs of Yalong Bay, sarcophytonolide M (20) was found as an undescribed cembranoid [4]. This isolate was inactive in the protein tyrosine phosphatase 1B (PTP1B) bioassay, a key target for the treatment of type-II diabetes and obesity. To search for more cembrane diterpenoids with PTP1B inhibitory activity, a much more detailed investigation of this specimen was conducted, resulting in the isolation of an array of cembranoids including undescribed sarcophytonolides N–Q (21–24) [25] and S–U (25–27) [26], together with known analogs cembrene-C (also termed as isoneocembrene, 16), (E,E,E)-1-isopropenyl-4,8,12-trimethylcyclotetradeca-3,7,11-triene (28) [25], sarcophytonolide A (29), and (E,E,E)-7,8-epoxy-l-isopropyl-4,8,12-trimethylcyclotetradeca-l,3,11-triene (30) [26]. For compounds 25 and 27, solution time-dependent density functional theory (TDDFT) calculations of ECD and specific rotation were applied in combination with conformational and NMR data analysis to determine their absolute configurations. Compounds 16 and 21–28 were tested for their inhibitory activity against PTP1B. The results revealed that sarcophytonolide N (21) showed significant activity with the IC50 value of 5.95 μM; compound 16 showed moderate activity (IC50 = 26.6 μM), while the remaining compounds 22–28 were inactive (IC50 > 20 μg/mL). None of the tested compounds (22–25, 28) exhibited cytotoxicity against two human cell lines A-549 and HL-60. To exploit the minor chemical constituents, research on the other two S. trocheliophorum specimens was carried out and yielded sarcophytrols D–L (31–39) [27,28], 11,12-epoxy-1(E),3(E),7(E)-cembratrien-15-ol (40), sinugibberol (41) [27], crassumol A (42) [28], sarglaucol (43) [29], 7R*,8R*-epoxy-isoneocembyance A-16-oic methyl ester (44), and 4-epithunbergol (45) [30]. None of the diterpenoids 31–43 showed PTP1B inhibitory effects in the bioassay. The cytotoxicity and acetylcholinesterase inhibitory bioassays of compounds 44 and 45 were also evaluated, and only 45 exhibited weak cytotoxicity against A-549 and HL-60 cell lines.
It was interesting to find that the Red Sea soft coral S. trocheliophorum produced compound 16 [16]. This cembratetraene was screened for a broad spectrum of biological activities including antibacterial, antifungal, cytotoxic, and antitumor effects. The antimicrobial bioassay revealed that 16 showed moderate activities against S. aureus MRSA, Micrococcus spp., S. pneumonia, and Acnietobacter spp. (the diameters of inhibition zones were 8–10 mm). Meanwhile, 16 had moderate antifungal activities against C. albicans, C. tropicals, A. flavus, and A. niger with diameters of inhibition zones ranging from 11 to 17 mm. Up to 13.6 μM, no toxicity was recorded against A. salina for 16. Additionally, 16 did not exhibit antitumor activities against the two tested lymphoma and Erlish cell lines. Another Red Sea collection afforded two new non-polar diterpenes, cis-cembrene C (46) and cis-cembrenene C (47) [17], and one known analog: (+)-sarcophytol A (48) [31]. These isolates were inactive against Bacillus subtilis, S. aureus, Streptomyces viridochromogenes (Tü 57), E. coli, C. albicans, Mucor miehi, Chlorella vulgaris, Chlorella sorokiniana, Scenedesmus subspicatus, Rhizoctonia solani, and Pythium ultimum at 40 μg/disk. They were further examined for cytotoxicity against brine shrimp at a concentration of 10 μg/mL (24 hr). Only cis-cembrene C (46) showed weak cytotoxicity with the mortality of 22.5%. This revealed that the hydroxyl group at C-14 and the exomethylene Δ15 were not necessary for the antifeedant property.
Recently, two new cembranoids, ximaosarcophytols A (49) and B (50), along with three related known ones, sarcophytrol J (37), crassumol A (42), and 15-hydroxycembra-1,3,7,11-tetraene (51), were found in the soft coral S. trocheliophorum collected from Ximao Island, South China Sea [32]. The absolute configurations of these two new compounds were elucidated using TDDFT/ECD calculations. All of the metabolites were subjected to various bioassays such as cytotoxic, inhibitory effects against demethylases ALKBH3 and FTO/ALKBH5, etc. However, all tested compounds showed only moderate to weak activities. The investigation of the specimen collected from the coast of the Xisha Islands in the South China Sea yielded 1,13-di-epi-13-acetoxy launine P (52), 13-oxo-thunbergol (53), and launine P (54) [33]. ECD calculations were also performed to assign the absolute configurations for new compounds 52 and 53. All of the isolates showed weak antibacterial activity against five pathogenic bacteria, S. aureus CMCC (B) 26003, methicillin-resistant S. aureus (MRSA) ATCC43300, B. subtilis CMCC (B) 63501, P. aeruginosa CMCC (B) 10104, and Salmonella paratyphi CMCC (B) 50071. Furthermore, all of these secondary metabolites were tested in vitro for antiviral activity against influenza A virus H1N1. Moderate anti-H1N1-virus activity was observed for terpenoids 53 and 54 (96.2% and 89.4% inhibition at 30 μM, respectively).

4.1.2. Furane Cembranoids

Records of furane cembranoids from S. trocheliophorum are rare, with only nine reported so far (Figure 6). According to the location of furan rings, they can be divided into two categories. Type I furane cembranoids possess an ether bridge between C-2 and C-16 while type II furane cembranoids have an ether bridge between C-1 and C-12.
In the first report of the chemical investigation of this species, sarcophytoxide (55) and isosarcophytoxide (56) were found in the Indonesian collection [3]. Compound 55 was also present in the Australian specimen collected from Orpheus Island [23], while 56 was disclosed in a Formosan sample collected in Kenting [34]. Compound 56 exhibited significant cytotoxicity against A-549, HT-29, KB, P-388, and HL-60 cells with ED50 values of 8.23, 8.27, 9.98, 0.49, and 0.80 μg/mL, respectively. A further study on a Formosan collection led to a cembranoid: 16-deoxysarcophine (57) [35]. Compound 57 showed potent cytotoxicity against A549, HT-29, and P-388 cells (ED50 = 15.74, 16.07, 3.87 μg/mL, respectively), but was inactive against the KB cell (ED50 > 50 μg/mL). A preliminary analysis of the structure–activity relationships revealed that the S configuration of H-2 decreased the cytotoxicity against the above-mentioned cells based on the comparison of furane cembranoids 56 and 57.
An investigation of the soft coral S. trocheliophorum collected off the cost of Hainan Island in the South China Sea resulted in (–)-sarcophytoxide (58) [30]. Compound 58 was inactive in the cytotoxicity and acetylcholinesterase inhibitory bioassays. An examination of another South China Sea specimen yielded sarcophytrols M–P (59–62) [29]. The modified Mosher method was applied to determine the absolute configuration of sarcophytrol M (59). Unfortunately, the bioassay results indicated that these metabolites exhibited no obvious bioactivities (PTP1B inhibitory activity, cytotoxicity against the human tumor cell lines HL-60 and K-562, antibacterial activity against P. aeruginosa).
Recently, a new cembrane diterpene, isocrassumol B (63), was encountered in a South China Sea sample collected on the Xisha Islands [33]. A pyran motif, rarely occurring between C-7 and C-11, was embodied in the structure of 63, in addition to the furan ring formed through C-2 and C-16. Its absolute configuration 2S,7R,8S,11R,12S was assigned using the ECD calculation. An antibacterial evaluation of 63 showed no activity against five pathogenic bacteria, S. aureus CMCC (B) 26003, methicillin-resistant S. aureus (MRSA) ATCC43300, B. subtilis CMCC (B) 63501, P. aeruginosa CMCC (B) 10104, and S. paratyphi CMCC (B) 50071. In addition, 63 did not exhibit in vitro antiviral activity against influenza A virus H1N1.

4.1.3. Pyrane Cembranoids

Pyrane-based cembranoids are also rare with only eleven members discovered up until now (Figure 7). Based on the different locations of the pyran rings, these metabolites can be categorized into three classes as follows: (type I) cyclized across C–2 and C-12; (type II) across C–1 and C-11; (type III) across C–12 and C-15.
Four new rare pyrane-based cembranoids, sarcotrocheliol acetate (64), and sarcotrocheliol (65) were isolated from the Red Sea soft coral S. trocheliophorum collected off the cost of Jeddah, Saudi Arabia [16]. It might be worth pointing out that the absolute configuration of sarcotrocheliol (65) was determined on the basis of a single crystal X-ray analysis in another investigation [36]. This result established the configuration revision of two chiral centers C-5 and C-14 as 5S,14R, which were misassigned in a previous report [16]. These two cembranoids were evaluated for a broad spectrum of biological activities including antibacterial, antifungal, antifeedant, and antitumor effects. The antimicrobial bioassay revealed that both compounds exhibited strong activities against S. aureus, S. epidermidis, S. aureus MRSA, Micrococcus spp., S. pneumonia, Acnietobacter spp., K. pneumonia, P. aeruginosa, and E. coli with diameters of inhibition zones ranging from 12 to 18 mm. However, none of them showed toxicity against A. salina or antitumor activity against lymphoma and Erlish cell lines up to 15.3 μM [16]. Continuous study on this specimen led to two additional new cembrane diterpenoids: sarcotrocheldiols A (66) and B (67) [37]. Only weak antibacterial activity was recorded for compounds 66 and 67 against the tested pathogenic bacteria including Acinetobacter baumannii, E. coli, K. pneumonia, P. aeruginosa, S. aureus, S. epidermidis, and S. pneumoniae. It seemed the E-geometry of Δ7 of pyrane cembranoids could increase the antibacterial activity.
In addition to three new cembranoids 9-hydroxy-10,11-dehydro-sarcotrocheliol (68) [31], 9-hydroxy-7,8-dehydro-sarcotrocheliol (69), and 8,9-expoy-sarcotrocheliol acetate (70) [38], sarcotrocheliol acetate (64) was also present in another Red Sea soft coral sample collected off the coast of Hurghada, Egypt. It is noteworthy that the absolute configurations of 69 were determined as 1S,4R,5S,9R,14R using single crystal X-ray analysis in another study [36]. This study revealed a reverse configuration at the three chiral centers C-1, C-4, and C-9, which was misassigned in a previous report [38]. All of the reported compounds showed no activity in the antimicrobial activity testing against S. aureus, B. subtilis ATCC6051, S. viridochromogenes Tü 57, E. coli, Mucor miehei Tü 284, C. albicans, and the green alga C. vulgaris at the concentration of 40 μg/disc [31,38]. The recollection of this soft coral off the Egyptian Red Sea coast afforded sarcotrocheliol (65) together with an unreported sarcopyranoid A (71) [39]. Compounds 65 and 71 displayed low cytotoxicity against A549 (IC50 67.5 ± 3.9, 79.9 ± 2.8 μg/mL, respectively). It appeared that the replacement of the olefinic bond at C-7/C-8 by an epoxide functionality did not cause the loss of the cytotoxicity for these two pyrane cembranoids. However, none of them exhibited detectable antileishmanial activity (IC50 > 100 μg/mL).
An examination of the South China Sea soft coral S. trocheliophorum disclosed three new bicyclic cembranoid sarcophytrols Q–S (72–74) [29]. Among them, sarcophytrols R (73) and S (74) shared a rare bicyclic skeleton of the decaryiol type. The bioassay results showed that none of them displayed PTP1B inhibitory activity or cytotoxicity against the human tumor cell lines HL-60 and K-562 or antibacterial activity against P. aeruginosa.

4.1.4. γ-Lactone Cembranoids

These metabolites can be regarded as the oxidation products of furane-based cembranoids. So far, fifteen diterpenoids of this type have been reported in S. trocheliophorum (Figure 8). According to the location of the γ-lactone ring, these cembranoids can be divided into two classes: ester linkage via C-2 and C-16 (type I) and via C-2 and C-18 (type II).
A cytotoxicity-guided fractionation of Formosan soft coral S. trocheliophorum yielded (+)-isosarcophine (75) [34]. This metabolite displayed potent cytotoxicity against A-549, HT-29, KB, P-388, and HL-60 cells with ED50 values of 13.32, 16.88, 24.54, 0.73, and 6.73 μg/mL, respectively. A further study on a Formosan sample led to the isolation of two cembranoids: 7β,8α-dihydroxydeepoxysarcophine (76) and sarcophine (77) [35]. Compounds 76 and 77 showed significant cytotoxicity against A549, HT-29, KB, and P-388 cells with ED50 values ranging from 2.42 to 24.66 μg/mL. It was interesting to find that the opening of the epoxide ring did not cause the loss of cytotoxicity against these cells for these two γ-lactone cembranoids. However, they were inactive against the KB cell (ED50 > 50 μg/mL), indicating their possible selective cytotoxicity. Interestingly, sarcophine (77) was distributed in many samples of different inhabiting environments such as Singaporean [8] and Saudi Arabian [16] waters. Compound 77 exhibited moderate growth inhibitory activity against the human HL60 leukemia cell (ED50 = 61.8 μg/mL) in the study on the Singaporean specimen [8]. Metabolite 77 was tested for antibacterial, antifungal, antifeedant, and antitumor effects in the research on a Saudi Arabian sample. The antimicrobial bioassay revealed that 77 showed moderate activities against S. aureus, S. epidermidis, S. aureus MRSA, Micrococcus spp., S. pneumonia, Acnietobacter spp., K. pneumonia, and E. coli with diameters of inhibition zones ranging from 8 to 12 mm. Meanwhile, 77 had moderate antifungal activities against C. albicans, C. tropicals, A. flavus, and A. niger (the diameters of inhibition zones were around 10 mm). Up to 9.4 μM, no toxicity was recorded against A. salina for the natural product 77. Additionally, 77 showed antitumor activities with LD50 values of 2.5 and 3.8 μM for the two tested lymphoma and Erlish cell lines, respectively [16].
An investigation of South China Sea soft coral S. trocheliophorum disclosed an unreported cembranoid (-)-sartrochine (78) [40]. Its relative stereochemistry was determined using X-ray diffraction analysis, and its absolute configuration was assigned using Cotton effects analysis. It displayed cytotoxic activity against S180 cells (IC50 = 12.3 μg/mL) and an antibiotic effect on Streptococcus hemolyticus (MIC = 14 μg/mL). Sarcophytonolides J (79) and R (80) were reported from another South China Sea sample [25]. The locations of γ-lactone on C-2, C-3, C-4, and C-18 were rare in cembranoids. In the PTP1B inhibitory bioassay, compounds 79 and 80 were inactive (IC50 ≥ 20 μg/mL). Additionally, none of them exhibited cytotoxicity against two human cell lines, A-549 and HL-60. Continuous study on the third South China Sea specimen led to the discovery of ent-sarcophine (81) and 2-hydroperoxysarcophine (82) [30]. The cytotoxicity against A-549 and HL-60 cell lines and acetylcholinesterase inhibitory bioassays of compounds 81 and 82 were evaluated, while only 81 exhibited weak acetylcholinesterase inhibitory activity. This result revealed that the hydroperoxide at C-2 might decrease the acetylcholinesterase inhibitory activity for γ-lactone cembranoids.
A new cembranoid, trocheliol (83), was isolated from the cultured soft coral S. trocheliophorum, which was originally collected off the coast of Pingtung, a southern Taiwan island [41,42]. It was noted that 83 was the first example of an α,β-unsaturated γ-lactone cembranoid possessing a tetrahydrofuran moiety with a rare 8,11-ether linkage. A hydroperoxycembranoidal diterpene trocheliolide A (84) [43] and its analog trocheliolide B (85) [44] were obtained from another Formosan soft coral S. trocheliophorum, which was collected off the cost of Lanyu Island. The cytotoxicity of trocheliolide A (84) against the proliferation of a limited panel of cancer cell lines, including MOLT-4 (human acute lymphoblastic leukemia), SUP-T1 (human T-cell lymphoblastic lymphoma), DLD-1 (human colorectal adenocarcinoma), LNCaP (human prostatic carcinoma), and MCF7 (human breast adenocarcinoma) was studied. The results showed that 84 was not cytotoxic against the above cancer cells (IC50 > 20 μg/mL).
An examination of the Egyptian specimen from the Gulf of Suez led to the discovery of a methyl ether derivative of 76, 7β-hydroxy-8α-methoxydeepoxysarcophine (86) [45]. A chemical investigation of another Egyptian sample from the coast of Hurghada resulted in the isolation of trochelioids A (87), B (88), 16-oxosarcophytonin E (89), and 8-epi-sarcophinone (90), together with two which were previously reported: sarcophine (77) and ent-sarcophine (81) [46]. Recently, a new cembranoid 7α,8α-sarcophine (91) and the known sarcophytonin B (92) were found in this species collected off the cost of the Xisha Islands, South China Sea [33]. ECD calculations were performed to determine the configuration of 7α,8α-sarcophine (91) as 2S,7R,8S. The antibacterial evaluations showed that only sarcophytonin B (92) exhibited a strong inhibition against S. aureus and B. subtilis (MIC < 0.5 μg/mL). The olefinic bond Δ7 of the γ-lactone cembranoid might play a crucial role in the antibacterial activity against the selected bacteria considering the decreased activity of compound 91 compared to that of 92. Unfortunately, both were inactive against influenza A virus H1N1.

4.1.5. ε-Lactone Cembranoids

Sixteen cembranoids possessing an α,β-unsaturated ε-lactone have been reported (Figure 9). These metabolites including eleven new compound sartrolides A–J (93–102) [26,47], together with seven known analogs, ketoemblide (103), 4Z,12Z,14E-sarcophytolide (104), sarcrassins D (105) and E (106), emblide (107), sarcophytolide (108), and deacetylemblide (109) [25,26,47], were obtained from the samples collected from the South China Sea. A solution TDDFT calculation of ECD was applied to determine the absolute configuration of 100 [26]. The absolute configurations of 104, 105, and 107 were assigned using the solid-state TDDFT-ECD approach and a single crystal X-ray diffraction experiment with Cu Kα radiation [26,47]. It is noteworthy that these diterpenoids shared the same R configuration at C-8, which was the joining point of the α,β-unsaturated ε-lactone moiety on the cembrane ring. Compounds 100, 103, and 104 showed potent PTP1B inhibitory activity (IC50 = 19.9, 27.2, 15.4 μM, respectively). The methyl ester of ε-lactone cembranoids might play an important role in the PTP1B inhibitory activity considering the increased activity of compound 100 compared to that of 95. Moreover, compounds 104 and 108 exhibited antibacterial activity against the methicillin-sensitive Staphylococcus aureus Newman strain (MIC = 250, 398 μM, respectively). A preliminary analysis of structure–activity relationships revealed that the ester group dramatically decreased the antibacterial activity for ε-lactone cembranoids based on the comparison of two pairs of 103/108 and 104/106. Unfortunately, none of them displayed cytotoxicity against two human A-549 and HL-60 cell lines.

4.1.6. Other Miscellaneous Cembranoids

Two new bicyclic cembranoids, sarcophytrols T (110) and U (111), were isolated from the South China Sea soft coral S. trocheliophorum [29] (Figure 10). Their chemical structures only differed at the patterns of the oxacycle (oxepane for 110 and peroxyl ring for 111). The absolute configuration of 110 was determined using the modified Mosher method. The PTP1B inhibitory, antitumor, and antibacterial activities were evaluated for these two diterpenoids. Unfortunately, none of them were active in the bioassays.

4.2. Perhydrophenanthrane Diterpenoid

Perhydrophenanthrane diterpenoid was extremely rare. So far, only one member (Figure 11), sarcophytin (112), was found in the soft coral S. trocheliophorum, which was collected off the coast of Madepam, Indian Ocean [15]. This compound was presumed to be the precursor of trocheliophorin (1). Unfortunately, no bioassay was performed on this diterpenoid.

4.3. Capnosane Diterpenoids

The basic skeleton of capnosane, a 5/11-fused bicyclic system, has been considered as a C-3/C-7 cyclization derivative of cembrane. Up until now, twenty-eight capnosane diterpenoids have been reported in this species (Figure 12).
Compound 113 was the first capnosane diterpene found in the soft coral S. trocheliophorum, which was collected from the Andaman and Nicobar Islands, Indian Ocean [48]. Only the stereochemistry at the ring junction, together with the E conformation of the trisubstituted double bond, were established. A chemical investigation of a South China Sea sample from Yalong Bay, Hainan Island, yielded two new capnosane diterpenoids, sarsolilides B (114) and C (115), and one known analog, sarsolilide A (116) [5]. The absolute configuration of 114 was determined using the TDDFT ECD calculation, which was further confirmed using a single crystal X-ray diffraction experiment with Cu Kα radiation [49]. Diterpenoids 114 and 116 showed PTP1B inhibitory activity, with IC50 values of 27.1 and 6.8 μM, respectively. The exomethylene Δ10(17) of the capnosane framework might play a crucial role in the PTP1B inhibitory activity considering the decreased activity of compounds 114 and 115 with respect to that of 116. Of more interest was the recognition of the stereochemistry of the hydroxyl group at C-10 by PTP1B. A compound with 10S configuration (in 114) was preferable to that with 10R configuration (in 115). A study on another Hainan specimen led to the discovery of three new capnosane type diterpenes: sarcophytrols A–C (117–119) [50]. Among them, 117 and 118 had an unusual 1Z-configuration double bond. Moreover, the absolute configuration of 117 was determined using X-ray diffraction analysis. In contrast to sarsolilide B (114), they were all inactive against the PTP1B enzyme. Regarding the structure–activity relationship of sarcophytrols, the lactone moiety of sarsolilide B (114) might be a key functional group.
Nineteen new capnosane cembranoids named trocheliophols A–S (120–138) together with sarcophytol L (139), 4-epi-sarcophytol L (140), and sarcophyolides B (141) and C (142) were isolated from the South China Sea soft coral S. trocheliophorum collected off the coast of Weizhou Island [6]. The absolute configurations of compounds 120, 121, 124, 125, 131, 132, 134, and 138 were determined using X-ray diffraction analysis, Snatzke’s method, and the modified Mosher method, respectively. In the bioassays for the inhibitory effects against inflammation-related NF-κB, metabolites 124, 125, and 132 showed weak inhibitory rates of 11%, 29%, and 14% at 10 μM. Moreover, compounds 127, 128, 131, 133, 134, and 137–140 exhibited antibacterial effects against Xanthomonas vesicatoria, Agrobacterium tumefaciens, Pseudomonas lachrymans, B. subtilis, and S. aureus, with MIC values ranging from 8 to 32 μg/mL. A preliminary analysis of the structure–activity relationships revealed that the exomethylene Δ8(19) of the capnosane skeleton enhanced the antibacterial activity. Moreover, compound 138, the only one with H-3β orientation, displayed the most potent inhibitory activity against the selected bacteria.

4.4. Sarsolenane Diterpenoids

To the best of our knowledge, only three sarsolenane diterpenoids [dihydrosarsolenone (143), methyl dihydrosarsolenoneate (144) and secodihydrosarsolenone (145), Figure 13 were isolated from a Chinese S. trocheliophorum sample collected in Yalong Bay, Hainan Island, South China Sea [5,51]. The assignment of absolute configuration of 143 was accomplished using the TDDFT ECD calculation. All of the metabolites were evaluated for inhibitory activity against PTP1B. Compound 145 exhibited PTP1B inhibitory activity with the IC50 value of 13.7 μM, whereas the other two were inactive (IC50 ≥ 50 μM). The ring cleavage of the α,β-unsaturated-β-ether ketone moiety in sarsolenane diterpenes might increase the PTP1B inhibitory activity due to the observation of considerable activity for 145 and no activity for 143 and 144. A computational calculation gave an insight into the binding mode. It suggested a crucial role of the residues Tyr46, Arg221, and Ser216 in ligand–receptor binding to fulfill the inhibitory activity of the metabolite 145 towards PTP1B.

4.5. Sarcotroane Diterpenoids

Two unprecedented diterpenoids, methyl sarcotroates A (146) and B (147) (Figure 14), possessed a tetradecahydrocyclopenta[3′,4′]cyclobuta[1′,2′:4,5]cyclonona[1,2-b] oxirene ring system, which was named a sarcotroane. Both were given by the Hainan soft coral S. trocheliophorum. The TDDFT ECD calculation approach was used to determine the absolute configuration of compound 146. Diterpenoid 147 exhibited significant inhibitory activity against PTP1B (IC50 = 6.97 μM), being similar to that of the positive control oleanolic acid [4]. This result indicated that the hydroperoxide group in the sarcotroane skeleton could enhance the PTP1B inhibitory activity.

5. Biscembranoids

Nine biscembranoids have been reported from the octocroal S. trocheliophorum (Figure 15). According to the different dimerization patterns, these biscembranoids could be divided into two types. The first type of cembrane dimers was formed by two cembranoid units connected through an ester linkage. The member of this category was bissartrolide (148), which was isolated from a South China Sea sample collected in Yalong Bay, Hainan Island [47]. Compound 148 was evaluated for antibacterial activity against the methicillin-sensitive S. aureus Newman strain, but it was inactive.
The second type of biscembranoid was dimerized via the Diels–Alder reaction with two monomers. Due to the structural diversity of the monomeric terpenes, this subgroup was further categorized by two different subclasses. The first carbon framework was trocheliane, which is named as it is merely one representative trocheliane (149). This compound was isolated from a Red Sea specimen and possessed an unprecedented tetracyclic hydrocarbon skeleton. This skeleton was proposed to be the Diels–Alder addition adduct of two cembrene-C (16) isomers accompanied with rearrangement and aromatization [37]. This hydrocarbon dimer showed promising activity against two multidrug resistant bacteria: A. baumannii and S. aureus (the diameters of inhibition zones were 18 ± 3.2, 18 ± 1.4 mm, respectively). The second framework was named glaucumane, the first two members of which were glaucumolides A (150) and B (151) from the soft coral Sarcophyton glaucum [52]. The proposed biosynthesis pathway of glaucumane biscembranoids was unique, which involved a ε-lactone cembrane as a diene monomer and a γ-lactone cembrane as a dienophile monomer. During the chemical investigation of a South China Sea soft coral S. trocheliophorum collected on the Xisha Islands, glaucumolides A (150) and B (151) and five new ones, bistrochelides A–E (152−156), were encountered [7]. Their absolute configurations were determined using X-ray crystal diffraction and TDDFT/ECD calculations. In in vitro immunomodulatory screening, compounds 150 and 154 significantly induced the proliferation of CD3+ T cells, while compound 152 significantly increased the CD4+/CD8+ ratio at 3.0 μM.

6. Conclusions

The abundant production and accumulation of terpenoids reported from the soft coral S. trocheliophorum is remarkable and intriguing. At present, 156 terpenoids have been encountered in the soft coral S. trocheliophorum, which indicates the productivity of this species. As shown in Table S1, the most typical terpenoids are macrocyclic cembrane diterpenes. Although other types of terpenoids are rarely encountered, they display a variety of unique carbon frameworks. Due to their novel structures, terpenoids from S. trocheliophorum, such as sarcophytin [53], are attractive targets for synthetic chemists.
It is interesting to notice that the chemical profiles of the title soft corals from different waters are different. For example, two S. trocheliophorum samples which grew in adjacent areas of the Red Sea (Jeddah, Saudi Arabia [16] and Hurgada, Egypt [17]) were afforded different chemotypes of sesquiterpenoids (Table S1). Moreover, the South China Sea S. trocheliophorum specimen yielded capnosane, sarsolenane, and sarcotroane diterpenoids [4,5] besides the common cembranoids [26], which were completely distinctive compared to that of the above-mentioned Red Sea sample [16]. In addition, the structural types of cembranoids from these two specimens were different. As reported, the ε-lactone and other miscellaneous cembranoids only existed in the South China Sea sample [25,26,29,47]. As shown in Figure 15, it was also obvious to find the influence of the geographical location on the types of biscembranoids. Two South China Sea specimens possessed bissartrane- [47] and glaucumane-type [7] biscembranoids, whereas the Red Sea specimen had a trocheliane-type biscembranoid. The impact of geographical location on the biscembranoids was also observed in the two South China Sea samples. The soft coral from Hainan Island afforded the bissartrane biscembranoid [47], while the one from the Xisha Islands yielded the glaucumane biscembranoids [7]. This probably reflects the existence of different metabolic processes in different inhabiting environments. Moreover, the impacts of temporal variations on the secondary metabolite production were also found. For instance, two South China Sea samples collected in Yalong Bay, Hainan Island, in different seasons (February [4], May [24], respectively) of the same year (Table S1), yielded diterpenes with completely distinct skeletons. Recently, Satheesh and Ba-Akdah also disclosed that the temporal variations significantly influenced the antifouling activity of the crude extracts of the soft coral S. trocheliophorum collected off the Jeddah coast of Saudi Arabia [54].
The terpenoids from S. trocheliophorum were screened for a vast array of potential pharmacological activities including PTP1B inhibitory, neuroprotective, cytotoxic, anti-inflammatory, antibacterial, antivirus, and immunomodulatory activities. As recorded in the literature, the majority of the reported compounds were inactive. These findings indicate that further substantial efforts are necessary to explore their unknown physiological roles.
Metabolites such as sarcophine (77) [16,35] and trocheliane (149) [37] exhibited significant biological activities, which could be developed as new drug leads. However, due to the low yields, a fairly large quantity of the coral organisms would be in demand. One way to accumulate the desired materials is to conduct heterologous expression of terpene biosynthetic genes for secondary metabolite production. Recently, Schmidt and co-workers found terpene synthase (TPS) genes in the genomes and transcriptomes of the soft coral S. trocheliophorum. In addition, the coral terpene cembrene-C (16) was successfully synthesized by incubating geranylgeranyl pyrophosphate (GGPP) with the purified coral enzyme EcTPS6 [55]. This work inspired us to explore more terpene biosynthetic gene clusters of this species, which might be in immense demand apart from the chemo- and bio-investigations.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/md21010030/s1: Table S1: Terpenoidal metabolites isolated from the soft coral Sarcophyton trocheliophorum.

Author Contributions

Conceptualization, L.-F.L.; investigation, Q.-B.Y. and J.-K.C.; writing—original draft preparation, Q.-B.Y.; writing—review and editing, Q.W. and L.-F.L.; supervision, L.-F.L.; funding acquisition, L.-F.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the National Natural Science Foundation of China (No. 41876194).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Liang, L.-F.; Guo, Y.-W. Terpenes from the soft corals of the genus Sarcophyton: Chemistry and biological activities. Chem. Biodivers 2013, 10, 2161–2196. [Google Scholar] [CrossRef] [PubMed]
  2. Elkhawas, Y.A.; Elissawy, A.M.; Elnaggar, M.S.; Mostafa, N.M.; Al-Sayed, E.; Bishr, M.M.; Singab, A.N.B.; Salama, O.M. Chemical diversity in species belonging to soft coral genus Sacrophyton and its impact on biological activity: A review. Mar. Drugs 2020, 18, 41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Tursch, B. Some recent developments in the chemistry of Alcyonaceans. Pure Appl. Chem. 1976, 48, 1–6. [Google Scholar] [CrossRef]
  4. Liang, L.-F.; Kurtán, T.; Mándi, A.; Yao, L.-G.; Li, J.; Zhang, W.; Guo, Y.-W. Unprecedented diterpenoids as a PTP1B inhibitor from the Hainan soft coral Sarcophyton trocheliophorum Marenzeller. Org. Lett. 2013, 15, 274–277. [Google Scholar] [CrossRef]
  5. Liang, L.-F.; Kurtán, T.; Mándi, A.; Gao, L.-X.; Li, J.; Zhang, W.; Guo, Y.-W. Sarsolenane and capnosane diterpenes from the Hainan soft coral Sarcophyton trocheliophorum Marenzeller as PTP1B inhibitors. Eur. J. Org. Chem. 2014, 2014, 1841–1847. [Google Scholar] [CrossRef]
  6. Liu, Z.; Cheng, W.; Liu, D.; van Ofwegen, L.; Proksch, P.; Lin, W. Capnosane-type cembranoids from the soft coral Sarcophyton trocheliophorum with antibacterial effects. Tetrahedron 2014, 70, 8703–8713. [Google Scholar] [CrossRef]
  7. Sun, P.; Cai, F.-Y.; Lauro, G.; Tang, H.; Su, L.; Wang, H.-L.; Li, H.H.; Mándi, A.; Kurtán, T.; Riccio, R.; et al. Immunomodulatory biscembranoids and assignment of their relative and absolute configurations: Data set modulation in the density functional theory/nuclear magnetic resonance approach. J. Nat. Prod. 2019, 82, 1264–1273. [Google Scholar] [CrossRef]
  8. Dong, H.; Gou, Y.-L.; Kini, R.M.; Xu, H.-X.; Chen, S.-X.; Teo, S.L.M.; But, P.P.-H. A new cytotoxic polyhydroxysterol from soft coral Sarcophyton trocheliophorum. Chem. Pharm. Bull. 2000, 48, 1087–1089. [Google Scholar] [CrossRef] [Green Version]
  9. Shaaban, M.; Ghani, M.A.; Shaaban, K.A. Zahramycins A-B, two new steroids from the coral Sarcophyton trocheliophorum. Z. Naturforsch. B—J. Chem. Sci. 2013, 68, 939–945. [Google Scholar] [CrossRef]
  10. Cai, F.; Sun, P.; Liu, B.; Tang, H.; Zhang, W. Sterols from the South China Sea soft coral Sarcophyton trocheliophorum. Guangdong Yaoxueyuan Xuebao 2014, 30, 36–39. [Google Scholar] [CrossRef]
  11. Chen, W.-T.; Liu, H.-L.; Yao, L.-G.; Guo, Y.-W. 9,11-Secosteroids and polyhydroxylated steroids from two South China Sea soft corals Sarcophyton trocheliophorum and Sinularia flexibilis. Steroids 2014, 92, 56–61. [Google Scholar] [CrossRef] [PubMed]
  12. Řezanka, T.; Dembitsky, V.M. γ-Lactones from the soft corals Sarcophyton trocheliophorum and Lithophyton arboreum. Tetrahedron 2001, 57, 8743–8749. [Google Scholar] [CrossRef]
  13. Gomaa, M.N.; Soliman, K.; Ayesh, A.; Abd El-Wahed, A.; Hamza, Z.; Mansour, H.M.; Khalifa, S.A.M.; Mohd Ali, H.B.; El-Seedi, H.R. Antibacterial effect of the red sea soft coral Sarcophyton trocheliophorum. Nat. Prod. Res. 2016, 30, 729–734. [Google Scholar] [CrossRef] [PubMed]
  14. Shaaban, M.; Ghani, M.A.; Issa, M.Y. New naturally occurring compounds from Sarcophyton trocheliophorum. Biointerface Res. App. Chem. 2022, 12, 2285–2331. [Google Scholar] [CrossRef]
  15. Anjaneyulu, A.S.R.; Rao, V.L.; Sastry, V.G.; Rao, D.V. Trocheliophorin: A novel rearranged sesquiterpenoid from the Indian Ocean soft coral Sarcophyton trocheliophorum. J. Asian Nat. Prod. Res. 2008, 10, 597–601. [Google Scholar] [CrossRef]
  16. Al-Footy, K.O.; Alarif, W.M.; Asiri, F.; Aly, M.M.; Ayyad, S.-E.N. Rare pyrane-based cembranoids from the Red Sea soft coral Sarcophyton trocheliophorum as potential antimicrobial–antitumor agents. Med. Chem. Res. 2015, 24, 505–512. [Google Scholar] [CrossRef]
  17. Shaaban, K.A.; Ghani, M.A.; Shaaban, M. New cembranoid diterpenes from Sarcophyton trocheliophorum. Br. J. Pharm. Res. 2015, 5, 192–201. [Google Scholar] [CrossRef]
  18. Groweiss, A.; Kashman, Y.; Vanderah, D.J.; Tursch, B.; Cornet, P.; Braekman, J.C.; Daloze, D. The structure of trocheliophorol, a cembranoid diterpene from soft corals of the genus Sarcophyton(1). Bull. Soc. Chim. Belg. 1978, 87, 277–283. [Google Scholar] [CrossRef]
  19. Carmely, S.; Groweiss, A.; Kashman, Y. Decaryiol, a new cembrane diterpene from the marine soft coral Sarcophyton decaryi. J. Org. Chem. 1981, 46, 4279–4284. [Google Scholar] [CrossRef]
  20. Coll, J.C.; Bowden, B.F.; Tapiolas, D.M.; Willis, R.H.; Djura, P.; Streamer, M.; Trott, L. Studies of Australian soft corals—XXXV: The terpenoid chemistry of soft corals and its implications. Tetrahedron 1985, 41, 1085–1092. [Google Scholar] [CrossRef]
  21. Suleimenova, A.M.; Kalinovskii, A.I.; Raldugin, V.A.; Shevtsov, S.A.; Bagryanskaya, I.Y.; Gatilov, Y.V.; Kuznetsova, T.A.; Elyakov, G.B. New derivatives of (−)-neocembrene from the soft coral Sarcophyton trocheliophorum. Chem. Nat. Compd. 1988, 24, 453–458. [Google Scholar] [CrossRef]
  22. Kuznetsova, T.A.; Popov, A.M.; Agafonova, I.G.; Suleimenova, A.M.; Elyakov, G.B. Physiological activity of diterpenoids from the soft coral Sarcophyton trocheliophorum. Chem. Nat. Compd. 1989, 25, 122–124. [Google Scholar] [CrossRef]
  23. Greenland, G.J.; Bowden, B.F. Cembranoid diterpenes related to sarcophytol A from the soft coral Sarcophyton trocheliophorum (Alcyonacea). Aust. J. Chem. 1994, 47, 2013–2021. [Google Scholar] [CrossRef]
  24. Yao, L.-G.; Zhang, H.-Y.; Liang, L.-F.; Guo, X.-J.; Mao, S.-C.; Guo, Y.-W. Yalongenes A and B, two new cembranoids with cytoprotective effects from the Hainan soft coral Sarcophyton trocheliophorum Marenzeller. Helv. Chim. Acta 2012, 95, 235–239. [Google Scholar] [CrossRef]
  25. Liang, L.-F.; Gao, L.-X.; Li, J.; Taglialatela-Scafati, O.; Guo, Y.-W. Cembrane diterpenoids from the soft coral Sarcophyton trocheliophorum Marenzeller as a new class of PTP1B inhibitors. Bioorg. Med. Chem. 2013, 21, 5076–5080. [Google Scholar] [CrossRef]
  26. Liang, L.-F.; Kurtán, T.; Mándi, A.; Yao, L.-G.; Li, J.; Lan, L.-F.; Guo, Y.-W. Structural, stereochemical, and bioactive studies of cembranoids from Chinese soft coral Sarcophyton trocheliophorum. Tetrahedron 2018, 74, 1933–1941. [Google Scholar] [CrossRef] [Green Version]
  27. Chen, W.-T.; Liang, L.-F.; Li, X.-W.; Xiao, W.; Guo, Y.-W. Further new highly oxidative cembranoids from the Hainan soft coral Sarcophyton trocheliophorum. Nat. Prod. Bioprospect. 2016, 6, 97–102. [Google Scholar] [CrossRef] [Green Version]
  28. Liang, L.-F.; Chen, W.-T.; Mollo, E.; Yao, L.-G.; Wang, H.-Y.; Xiao, W.; Guo, Y.-W. Sarcophytrols G–L, novel minor metabolic components from South China Sea soft coral Sarcophyton trocheliophorum Marenzeller. Chem. Biodivers. 2017, 14, e1700079. [Google Scholar] [CrossRef]
  29. Liang, L.-F.; Chen, W.-T.; Li, X.-W.; Wang, H.-Y.; Guo, Y.-W. New bicyclic cembranoids from the South China Sea soft coral Sarcophyton trocheliophorum. Sci. Rep. 2017, 7, 46584. [Google Scholar] [CrossRef] [Green Version]
  30. He, L.-L.; Liu, H.-L.; Liang, L.-F.; Zhang, H.-B.; Guo, Y.-W. Studies on chemical constituents of Sarcophyton trocheliophrum. Chin. J. Mar. Drugs 2013, 32, 37–40. [Google Scholar] [CrossRef]
  31. Shaaban, M.; Ghani Mohamed, A.; Shaaban Khaled, A. Unusual pyranosyl cembranoid diterpene from Sarcophyton trocheliophorum. Z. Naturforsch. B-J. Chem. Sci. 2016, 71, 1211–1217. [Google Scholar] [CrossRef]
  32. Chen, Z.-H.; Gao, T.-R.; Yang, M.; Yao, L.-G.; Guo, Y.-W. Further new cembranoids from the South China Sea soft coral Sarcophyton trocheliophorum. Fitoterapia 2021, 151, 104902. [Google Scholar] [CrossRef] [PubMed]
  33. Ren, L.; Leng, X.; Li, T.; Liu, J.; Wang, W.; Yan, X.; Yan, X.; He, S. Four new cembranoids from the South China Sea soft coral Sarcophyton trocheliophorum. Nat. Prod. Res. 2022. [Google Scholar] [CrossRef] [PubMed]
  34. Wu, Y.-C.; Hsieh, P.-W.; Duh, C.-Y.; Wang, S.-K.; Soong, K.-Y.; Fang, L.-S. Studies on the Formosan soft corals I-Cytotoxic cembrane diterpenes from Sarcophyton trocheliophorum. J. Chin. Chem. Soc. 1992, 39, 355–357. [Google Scholar] [CrossRef]
  35. Duh, C.-Y.; Hou, R.-S. Cytotoxic cembranoids from the soft corals Sinularia gibberosa and Sarcophyton trocheliophorum. J. Nat. Prod. 1996, 59, 595–598. [Google Scholar] [CrossRef]
  36. Hamed, A.; Issa, M.Y.; Ghani, M.A.; Frese, M.; Neumann, B.; Stammler, H.G.; Sewald, N.; Shaaban, M. Crystal structure and configuration revision of 9-hydroxy-7,8-dehydro-sarcotrocheliol and sarcotrocheliol. Nat. Prod. Res. 2019, 33, 3029–3032. [Google Scholar] [CrossRef]
  37. Zubair, M.; Alarif, W.; Al-Footy, K.; Mohamed, P.H.; Ali, M.; Basaif, S.; Al-Lihaibi, S.; Ayyad, S.-E. New antimicrobial biscembrane hydrocarbon and cembranoid diterpenes from the soft coral Sarcophyton trocheliophorum. Turk. J. Chem. 2016, 40, 385–392. [Google Scholar] [CrossRef]
  38. Shaaban, M.; Issa, M.Y.; Ghani, M.A.; Hamed, A.; Abdelwahab, A.B. New pyranosyl cembranoid diterpenes from Sarcophyton trocheliophorum. Nat. Prod. Res. 2019, 33, 24–33. [Google Scholar] [CrossRef]
  39. Zidan, S.A.H.; Abdelhamid, R.A.; Alian, A.; Fouad, M.A.; Matsunami, K.; Orabi, M.A.A. Diterpenes and sterols from the Red Sea soft coral Sarcophyton trocheliophorum and their cytotoxicity and anti-leishmanial activities. J. Asian Nat. Prod. Res. 2022, 24, 794–802. [Google Scholar] [CrossRef]
  40. Su, J.-Y.; Zhong, Y.-L.; Lou, G.-X.; Li, X.-Q.; Zeng, L.-M.; Huang, Y.-Q.; Hu, S.-Z. Studies on the stereochemistry of (-)-sartrochine. Acta Chim. Sinica 1994, 52, 813–816. [Google Scholar]
  41. Su, J.-H.; Lu, Y.; Lin, W.-Y.; Wang, W.-H.; Sung, P.-J.; Sheu, J.-H. A cembranoid, trocheliophorol, from the cultured soft coral Sarcophyton trocheliophorum. Chem. Lett. 2010, 39, 172–173. [Google Scholar] [CrossRef]
  42. Su, J.-H.; Lu, Y.; Lin, W.-Y.; Wang, W.-H.; Sung, P.-J.; Sheu, J.-H. A cembranoid, trocheliophorol, from the cultured soft coral Sarcophyton trocheliophorum. Chem. Lett. 2012, 41, 340. [Google Scholar] [CrossRef]
  43. Liu, K.-M.; Cheng, C.-H.; Chen, W.-F.; Lu, M.-C.; Fang, L.-S.; Wen, Z.-H.; Su, J.-H.; Wu, Y.-C.; Sung, P.-J. Trocheliolide A, a hydroperoxycembranoidal diterpene from the octocoral Sarcophyton trocheliophorum. Nat. Prod. Commun. 2015, 10, 1163–1165. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Liu, K.-M.; Lan, Y.-H.; Su, C.-C.; Sung, P.-J. Trocheliolide B, a new cembranoidal diterpene from the octocoral Sarcophyton trocheliophorum. Nat. Prod. Commun. 2016, 11, 21–22. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Grote, D.; Soliman, H.S.M.; Shaker, K.H.; Hamza, M.; Seifert, K. Cembranoid diterpenes and a briarane diterpene from corals. Nat. Prod. Res. 2006, 20, 285–291. [Google Scholar] [CrossRef]
  46. Hegazy, M.-E.F.; Mohamed, T.A.; Abdel-Latif, F.F.; Alsaid, M.S.; Shahat, A.A.; Paré, P.W. Trochelioid A and B, new cembranoid diterpenes from the Red Sea soft coral Sarcophyton trocheliophorum. Phytochem. Lett. 2013, 6, 383–386. [Google Scholar] [CrossRef]
  47. Liang, L.-F.; Lan, L.-F.; Taglialatela-Scafati, O.; Guo, Y.-W. Sartrolides A-G and bissartrolide, new cembranolides from the South China Sea soft coral Sarcophyton trocheliophorum Marenzeller. Tetrahedron 2013, 69, 7381–7386. [Google Scholar] [CrossRef]
  48. Venkateswarlu, Y.; Chavakula, R.; Biabani, M.A.F.; Rao, T.P. A new diterpene from a soft coral Sarcophyton trocheliphorum. Nat. Prod. Lett. 1994, 5, 131–134. [Google Scholar] [CrossRef]
  49. Zhu, J.-Y.; Li, W.; Bao, J.-M.; Zhang, J.-S.; Yin, S.; Tang, G.-H. Diterpenoids from the South China Sea soft coral Sarcophyton solidum. Biochem. Syst. Ecol. 2015, 62, 6–10. [Google Scholar] [CrossRef]
  50. Chen, W.-T.; Yao, L.-G.; Li, X.-W.; Guo, Y.-W. Sarcophytrols A–C, new capnosane diterpenoids from the South China Sea soft coral Sarcophyton trocheliophorum. Tetrahedron Lett. 2015, 56, 1348–1352. [Google Scholar] [CrossRef]
  51. Liang, L.-F.; Wang, J.-A.; Shi, X.-X.; Zhu, Y.-H.; Li, J.; Zhu, W.-L.; Wang, H.-Y.; Guo, Y.-W. A novel sarsolenane diterpene as a PTP1B inhibitor from Hainan soft coral Sarcophyton trocheliophorum Marenzeller. Chin. J. Chem. 2017, 35, 1246–1250. [Google Scholar] [CrossRef]
  52. Huang, C.-Y.; Sung, P.-J.; Uvarani, C.; Su, J.-H.; Lu, M.-C.; Hwang, T.-L.; Dai, C.-F.; Wu, S.-L.; Sheu, J.-H. Glaucumolides A and B, biscembranoids with new structural type from a cultured soft coral Sarcophyton glaucum. Sci. Rep. 2015, 5, 15624. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. He, C.; Xuan, J.; Rao, P.; Xie, P.-P.; Hong, X.; Lin, X.; Ding, H. Total syntheses of (+)-sarcophytin, (+)-chatancin, (−)-3-oxochatancin, and (−)-pavidolide B: A divergent approach. Angew. Chem. Int. Ed. 2019, 58, 5100–5104. [Google Scholar] [CrossRef] [PubMed]
  54. Satheesh, S.; Ba-Akdah, M.A. Temporal variations in the antifouling activity of extract of the soft coral Sarcophyton trocheliophorum collected from the Red Sea. Ocean Sci. J. 2022, 57, 247–258. [Google Scholar] [CrossRef]
  55. Scesa, P.D.; Lin, Z.; Schmidt, E.W. Ancient defensive terpene biosynthetic gene clusters in the soft corals. Nat. Chem. Biol. 2022, 18, 659–663. [Google Scholar] [CrossRef] [PubMed]
Marinedrugs 21 00030 g001 550
Figure 1. Terpenoidal skeletons from S. trocheliophorum.
Figure 1. Terpenoidal skeletons from S. trocheliophorum.
Marinedrugs 21 00030 g001
Marinedrugs 21 00030 g002 550
Figure 2. Reported bioactivities of the terpenoids from S. trocheliophorum.
Figure 2. Reported bioactivities of the terpenoids from S. trocheliophorum.
Marinedrugs 21 00030 g002
Marinedrugs 21 00030 g003 550
Figure 3. Structures of compounds 1–6, sesquiterpenoids from S. trocheliophorum.
Figure 3. Structures of compounds 1–6, sesquiterpenoids from S. trocheliophorum.
Marinedrugs 21 00030 g003
Marinedrugs 21 00030 g004 550
Figure 4. Diterpenoids from S. trocheliophorum with different structural types.
Figure 4. Diterpenoids from S. trocheliophorum with different structural types.
Marinedrugs 21 00030 g004
Marinedrugs 21 00030 g005 550
Figure 5. Structures of compounds 7–54, isopropyl/isopropenyl cembranoids from S. trocheliophorum.
Figure 5. Structures of compounds 7–54, isopropyl/isopropenyl cembranoids from S. trocheliophorum.
Marinedrugs 21 00030 g005
Marinedrugs 21 00030 g006 550
Figure 6. Structures of compounds 55–63, furane cembranoids from S. trocheliophorum.
Figure 6. Structures of compounds 55–63, furane cembranoids from S. trocheliophorum.
Marinedrugs 21 00030 g006
Marinedrugs 21 00030 g007 550
Figure 7. Structures of compounds 64–74, pyrane cembranoids from S. trocheliophorum.
Figure 7. Structures of compounds 64–74, pyrane cembranoids from S. trocheliophorum.
Marinedrugs 21 00030 g007
Marinedrugs 21 00030 g008 550
Figure 8. Structures of compounds 75–92, γ-lactone cembranoids from S. trocheliophorum.
Figure 8. Structures of compounds 75–92, γ-lactone cembranoids from S. trocheliophorum.
Marinedrugs 21 00030 g008
Marinedrugs 21 00030 g009 550
Figure 9. Structures of compounds 93–109, ε-lactone cembranoids from S. trocheliophorum.
Figure 9. Structures of compounds 93–109, ε-lactone cembranoids from S. trocheliophorum.
Marinedrugs 21 00030 g009
Marinedrugs 21 00030 g010 550
Figure 10. Structures of compounds 110 and 111, other miscellaneous cembranoids from S. trocheliophorum.
Figure 10. Structures of compounds 110 and 111, other miscellaneous cembranoids from S. trocheliophorum.
Marinedrugs 21 00030 g010
Marinedrugs 21 00030 g011 550
Figure 11. Structure of compound 112, perhydrophenanthrane diterpenoid from S. trocheliophorum.
Figure 11. Structure of compound 112, perhydrophenanthrane diterpenoid from S. trocheliophorum.
Marinedrugs 21 00030 g011
Marinedrugs 21 00030 g012 550
Figure 12. Structures of compounds 113–142, capnosane diterpenoids from S. trocheliophorum.
Figure 12. Structures of compounds 113–142, capnosane diterpenoids from S. trocheliophorum.
Marinedrugs 21 00030 g012
Marinedrugs 21 00030 g013 550
Figure 13. Structures of compounds 143–145, sarsolenane diterpenoids from S. trocheliophorum.
Figure 13. Structures of compounds 143–145, sarsolenane diterpenoids from S. trocheliophorum.
Marinedrugs 21 00030 g013
Marinedrugs 21 00030 g014 550
Figure 14. Structures of compounds 146 and 147, sarcotroane diterpenoids from S. trocheliophorum.
Figure 14. Structures of compounds 146 and 147, sarcotroane diterpenoids from S. trocheliophorum.
Marinedrugs 21 00030 g014
Marinedrugs 21 00030 g015 550
Figure 15. Structures of compounds 148–156, biscembranoids from S. trocheliophorum.
Figure 15. Structures of compounds 148–156, biscembranoids from S. trocheliophorum.
Marinedrugs 21 00030 g015
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Yang, Q.-B.; Wu, Q.; Chen, J.-K.; Liang, L.-F. The Soft Coral Sarcophyton trocheliophorum: A Warehouse of Terpenoids with Structural and Pharmacological Diversity. Mar. Drugs 2023, 21, 30. https://doi.org/10.3390/md21010030

AMA Style

Yang Q-B, Wu Q, Chen J-K, Liang L-F. The Soft Coral Sarcophyton trocheliophorum: A Warehouse of Terpenoids with Structural and Pharmacological Diversity. Marine Drugs. 2023; 21(1):30. https://doi.org/10.3390/md21010030

Chicago/Turabian Style

Yang, Qi-Bin, Qihao Wu, Jun-Kun Chen, and Lin-Fu Liang. 2023. "The Soft Coral Sarcophyton trocheliophorum: A Warehouse of Terpenoids with Structural and Pharmacological Diversity" Marine Drugs 21, no. 1: 30. https://doi.org/10.3390/md21010030

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop