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Natural Products and Analogues with Promising Biological Profiles

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 3878

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Special Issue Editor

Dr. Kristina Starčević

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Guest Editor

Department of Chemistry and Biochemistry, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, HR-10000 Zagreb, Croatia
Interests: medicinal chemistry; nutraceuticals; bioactive compounds; metabolic diseases; lipidomics; nutrition; antioxidants

Special Issue Information

Dear Colleagues,

Through the ages, humans have relied on nature to meet their needs, including as a source of medicines. The first records of sophisticated traditional medical practises date back to roughly 2600 BCE, with plants serving as the foundation. Nowadays, the discovery of novel chemical entities for therapeutic use as well as the development of new and more potent pharmaceuticals rely heavily on natural products. Natural products represent an invaluable foundation for the development of potential lead compounds in contemporary drug discovery. It is noteworthy that only 36% of the novel chemical entities found between 1981 and 2015 were not inspired by a natural product, according to an examination of the origins of new medications during that time period.

Natural products have very complex structures that make their syntheses intrinsically challenging; therefore, natural product analogue libraries are much smaller than commercial ones. The structures of natural compounds comprise a broad variety of biologically relevant chemical spaces, and synthetic compounds in commonly accessible screening libraries cannot be used to efficiently investigate them. However, only minor chemical changes are needed to obtain the further drugability of natural compouds structurally fine-tuned by nature for optimum bioactivity.

This Special Issue aims to compile research papers that will provide an overview of the various classes of natural products, such as advancements in the chemistry and biology of natural products, interactions with the environment, and the importance of plant-based natural products for humans. Studies with a focus on advancements in the utilisation of small-molecule natural-product-derived privileged scaffolds with prominent biological activity and clinical potential will also be highlighted.

Dr. Kristina Starčević
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

natural products
bioactive compounds
insect abstracts
marine derived product
medicinal plants
secondary metabolites
chemical ecology

Published Papers (6 papers)

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Research

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28 pages, 5224 KiB

Open AccessArticle

Exploring the Antiproliferative and Modulatory Effects of 1-Methoxyisobrassinin on Ovarian Cancer Cells: Insights into Cell Cycle Regulation, Apoptosis, Autophagy, and Its Interactions with NAC

by Martina Zigová, Viktória Miškufová, Marianna Budovská, Radka Michalková and Ján Mojžiš

Molecules 2024, 29(8), 1773; https://doi.org/10.3390/molecules29081773 - 13 Apr 2024

Viewed by 389

Abstract

Ovarian cancer, a highly lethal malignancy among reproductive organ cancers, poses a significant challenge with its high mortality rate, particularly in advanced-stage cases resistant to platinum-based chemotherapy. This study explores the potential therapeutic efficacy of 1-methoxyisobrassinin (MB-591), a derivative of indole phytoalexins found in Cruciferae family plants, on both cisplatin-sensitive (A2780) and cisplatin-resistant ovarian cancer cells (A2780 cis). The findings reveal that MB-591 exhibits an antiproliferative effect on both cell lines, with significantly increased potency against cisplatin-sensitive cells. The substance induces alterations in the distribution of the cell cycle, particularly in the S and G2/M phases, accompanied by changes in key regulatory proteins. Moreover, MB-591 triggers apoptosis in both cell lines, involving caspase-9 cleavage, PARP cleavage induction, and DNA damage, accompanied by the generation of reactive oxygen species (ROS) and mitochondrial dysfunction. Notably, the substance selectively induces autophagy in cisplatin-resistant cells, suggesting potential targeted therapeutic applications. The study further explores the interplay between MB-591 and antioxidant N-acetylcysteine (NAC), in modulating cellular processes. NAC demonstrates a protective effect against MB-591-induced cytotoxicity, affecting cell cycle distribution and apoptosis-related proteins. Additionally, NAC exhibits inhibitory effects on autophagy initiation in cisplatin-resistant cells, suggesting its potential role in overcoming resistance mechanisms. Full article

(This article belongs to the Special Issue Natural Products and Analogues with Promising Biological Profiles)

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17 pages, 2028 KiB

Open AccessArticle

Synergetic Effects of Aloe Vera Extract with Trimethylglycine for Targeted Aquaporin 3 Regulation and Long-Term Skin Hydration

by Viktor Filatov, Anna Sokolova, Natalya Savitskaya, Mariya Olkhovskaya, Andrey Varava, Egor Ilin and Elizaveta Patronova

Molecules 2024, 29(7), 1540; https://doi.org/10.3390/molecules29071540 - 29 Mar 2024

Viewed by 589

Abstract

Aquaporin 3 (AQP3) channels are tetrameric membrane-bound channels that facilitate the transport of water and other small solutes across cell membranes in the skin. Decreased AQP3 expression is associated with skin dryness, skin aging, psoriasis, and delayed wound healing. Thus, our study focused on a novel combination based on Aloe barbadensis leaf extract and trimethylglycine for targeted AQP3 regulation in skin keratinocytes and deep skin moisturization. Firstly, a dose-finding cytotoxicity assay of the selected substances was performed with a 2,5-diphenyl-2H-tetrazolium bromide (MTT) indicator on HaCaT cells. The substances’ ability to increase the amount of AQP3 in keratinocytes was evaluated in a keratinocyte cell culture by means of ELISA. Additionally, the deep skin hydration effect was confirmed in clinical research with healthy volunteers. According to the results, the maximum tolerated doses providing viability at 70% (MTD_s) values for Aloe barbadensis leaf extract and trimethylglycine were 24.50% and 39.00%, respectively. Following the research and development, a complex based on Aloe barbadensis leaf extract and trimethylglycine in a 1:1 mass ratio exhibited a good cytotoxicity profile, with an MTD_s value of 37.90%. Furthermore, it was shown that the combination had a clear synergetic effect and significantly increased AQP3 by up to 380% compared to the negative control and glyceryl glucoside (p < 0.001). It was clinically confirmed that the developed shower gel containing Aloe barbadensis leaf extract and trimethylglycine safely improved skin hydration after one use and over 28 days. Thus, this novel plant-based combination has promising potential for AQP3 regulation in the skin epidermis and a role in the development of dermatological drugs for the treatment of skin xerosis and atopic-related conditions. Full article

(This article belongs to the Special Issue Natural Products and Analogues with Promising Biological Profiles)

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19 pages, 5283 KiB

Open AccessArticle

Mode of Antibacterial Action of Tomatidine C3-Diastereoisomers

by Jean-Philippe Langlois, Audrey Larose, Eric Brouillette, Julien A. Delbrouck, Pierre-Luc Boudreault and François Malouin

Molecules 2024, 29(2), 343; https://doi.org/10.3390/molecules29020343 - 10 Jan 2024

Viewed by 710

Abstract

Tomatidine (TO) is a natural narrow-spectrum antibiotic acting on the Staphylococcus aureus small colony variant (SCV) with a minimal inhibitory concentration (MIC) of 0.06 µg/mL while it shows no activity against prototypical strains (MIC > 128 µg/mL). To expand the spectrum of activity of TO, the 3β-hydroxyl group was substituted with an ethane-1,2-diamine, resulting in two diastereoisomers, TM-02 (C3-β) and TM-03 (C3-α). These molecules are equally potent against prototypical S. aureus and E. coli strains (MIC 8 and 32 µg/mL, respectively), whereas TM-02 is more potent against SCV (MIC 0.5 µg/mL) and hyperpermeable E. coli strains (MIC 1 µg/mL). The differences in their modes of action were investigated. We used membrane vesicles to confirm the inhibition of the bacterial ATP synthase, the documented target of TO, and measured effects on bacterial cell membranes. Both molecules inhibited E. coli ATP synthase, with K_i values of 1.1 µM and 3.5 µM for TM-02 and TM-03, respectively, and the bactericidal effect of TM-02 was linked to ATP synthase inhibition. Furthermore, TM-02 had no major effect on the membrane fluidity and gradually reduced membrane potential. In contrast, TM-03 caused structural damages to membranes and completely disrupted the membrane potential (>90%). We were successful in broadening the spectrum of activity of TO. C3-β-diastereoisomers may have more specific antibacterial action than C3-α. Full article

(This article belongs to the Special Issue Natural Products and Analogues with Promising Biological Profiles)

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25 pages, 8398 KiB

Open AccessArticle

Anti-Inflammatory Properties of Eugenol in Lipopolysaccharide-Induced Macrophages and Its Role in Preventing β-Cell Dedifferentiation and Loss Induced by High Glucose-High Lipid Conditions

by Esmaeel Ghasemi Gojani, Bo Wang, Dong-Ping Li, Olga Kovalchuk and Igor Kovalchuk

Molecules 2023, 28(22), 7619; https://doi.org/10.3390/molecules28227619 - 16 Nov 2023

Viewed by 1094

Abstract

Inflammation is a natural immune response to injury, infection, or tissue damage. It plays a crucial role in maintaining overall health and promoting healing. However, when inflammation becomes chronic and uncontrolled, it can contribute to the development of various inflammatory conditions, including type 2 diabetes. In type 2 diabetes, pancreatic β-cells have to overwork and the continuous impact of a high glucose, high lipid (HG-HL) diet contributes to their loss and dedifferentiation. This study aimed to investigate the anti-inflammatory effects of eugenol and its impact on the loss and dedifferentiation of β-cells. THP-1 macrophages were pretreated with eugenol for one hour and then exposed to lipopolysaccharide (LPS) for three hours to induce inflammation. Additionally, the second phase of NLRP3 inflammasome activation was induced by incubating the LPS-stimulated cells with adenosine triphosphate (ATP) for 30 min. The results showed that eugenol reduced the expression of proinflammatory genes, such as IL-1β, IL-6 and cyclooxygenase-2 (COX-2), potentially by inhibiting the activation of transcription factors NF-κB and TYK2. Eugenol also demonstrated inhibitory effects on the levels of NLRP3 mRNA and protein and Pannexin-1 (PANX-1) activation, eventually impacting the assembly of the NLRP3 inflammasome and the production of mature IL-1β. Additionally, eugenol reduced the elevated levels of adenosine deaminase acting on RNA 1 (ADAR1) transcript, suggesting its role in post-transcriptional mechanisms that regulate inflammatory responses. Furthermore, eugenol effectively decreased the loss of β-cells in response to HG-HL, likely by mitigating apoptosis. It also showed promise in suppressing HG-HL-induced β-cell dedifferentiation by restoring β-cell-specific biomarkers. Further research on eugenol and its mechanisms of action could lead to the development of therapeutic interventions for inflammatory disorders and the preservation of β-cell function in the context of type 2 diabetes. Full article

(This article belongs to the Special Issue Natural Products and Analogues with Promising Biological Profiles)

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Review

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14 pages, 2872 KiB

Open AccessReview

Azulene and Its Derivatives as Potential Compounds in the Therapy of Dermatological and Anticancer Diseases: New Perspectives against the Backdrop of Current Research

by Emilia Slon, Bartosz Slon and Dorota Kowalczuk

Molecules 2024, 29(9), 2020; https://doi.org/10.3390/molecules29092020 - 27 Apr 2024

Viewed by 209

Abstract

The scientific article focuses on the role of azulene and its derivatives in the therapy of dermatological diseases, presenting the latest laboratory and clinical research as well as prospects for further studies. In a synthetic literature review, various databases such as PubMed, Scopus, Web of Science, and the Database of Polish Scientific Journals were queried to select relevant articles concerning azulene. The conclusions drawn from the thematic analysis of the studies emphasize the multifaceted pharmacological actions of azulene and its derivatives including their anti-inflammatory properties, potential anticancer effects, photoprotective abilities, alleviation of itching, management of atopic dermatitis, and treatment of erectile dysfunction. However, there are certain limitations associated with the application of unmodified azulene on the skin, particularly related to photodecomposition and the generation of reactive oxygen species under UV radiation. These effects, in turn, necessitate further research on the safety of azulene and azulene-derived substances, especially regarding their long-term use and potential application in phototherapy. The authors of this work emphasize the necessity of conducting further preclinical and clinical studies to fully understand the mechanisms of action. Incorporating azulene and its derivatives into the therapy of dermatological disorders may represent an innovative approach, thereby opening new treatment avenues for patients. Full article

(This article belongs to the Special Issue Natural Products and Analogues with Promising Biological Profiles)

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0 pages, 2189 KiB

Open AccessReview

Wondrous Yellow Molecule: Are Hydrogels a Successful Strategy to Overcome the Limitations of Curcumin?

by Magdalena Stachowiak, Dariusz T. Mlynarczyk and Jolanta Dlugaszewska

Molecules 2024, 29(8), 1757; https://doi.org/10.3390/molecules29081757 - 12 Apr 2024

Viewed by 460

Abstract

Curcumin is a natural compound with a great pharmaceutical potential that involves anticancer, anti-inflammatory, antioxidant, and neuroprotective activity. Unfortunately, its low bioavailability, instability, and poor water solubility significantly deteriorate its clinical use. Many attempts have been made to overcome this issue, and encapsulating curcumin in a hydrogel matrix may improve those properties. Hydrogel formulation is used in many drug delivery forms, including classic types and novel forms such as self-assembly systems or responsive to external factors. Reviewed studies confirmed better properties of hydrogel-stabilized curcumin in comparison to pure compound. The main enhanced characteristics were chemical stability, bioavailability, and water solubility, which enabled these systems to be tested for various diseases. These formulations were evaluated for wound healing properties, effectiveness in treating skin diseases, and anticancer and regenerative activity. Hydrogel formulation significantly improved biopharmaceutical properties, opening the opportunity to finally see curcumin as a clinically approved substance and unravel its therapeutic potential. Full article

(This article belongs to the Special Issue Natural Products and Analogues with Promising Biological Profiles)

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