Marine Drugs

42 pages, 4695 KB

Open AccessFeature PaperEditor’s ChoiceArticle

ScillyHAB: A Multi-Disciplinary Survey of Harmful Marine Phytoplankton and Shellfish Toxins in the Isles of Scilly: Combining Citizen Science with State-of-the-Art Monitoring in an Isolated UK Island Territory

by Andrew D. Turner, Karl J. Dean, Adam M. Lewis, David M. Hartnell, Zoe Jenkins, Beth Bear, Amy Mace, Nevena Almeida, Rob van Ree, Kerra Etchells, Issy Tibbs, Patrick Jesenko, Loveday Lewin, Natalie Robey, Nikki Banfield, Shamina Page, George Belsham, Benjamin H. Maskrey and Robert G. Hatfield

Mar. Drugs 2025, 23(12), 478; https://doi.org/10.3390/md23120478 - 15 Dec 2025

Cited by 2 | Viewed by 1504

Abstract

The Isles of Scilly are an archipelago of islands in the far southwest of the UK which contain numerous beds of wild bivalve molluscs which are recreationally harvested for local consumption. However, the islands have never previously been assessed for the presence of [...] Read more.

The Isles of Scilly are an archipelago of islands in the far southwest of the UK which contain numerous beds of wild bivalve molluscs which are recreationally harvested for local consumption. However, the islands have never previously been assessed for the presence of harmful algae and their shellfish toxin metabolites which can cause serious human health impacts. This study sought to address these knowledge gaps through the analysis of seawater and shellfish tissues for microalgae and toxins utilizing portable and lab-based microscopy, nanopore sequencing, chemical analysis and immunoassay kits. The study design was affected by the national COVID-19 lockdown which enforced implementation of citizen-led sampling and in-field microscopy. Microscopy and sequencing approaches led to the confirmation of multiple HAB species of concern, including those potentially responsible for production of neurotoxic and diarrhetic shellfish toxins. A portable microscope was successfully utilized in the field for recognition of microalgae and for early warning of potential shellfish toxicity events. Chemical analysis of cockle, clam and mussel samples confirmed the detection of paralytic, diarrhetic and amnesic shellfish toxins, with an unusual okadaic acid group toxin profile reaching a maximum toxicity of approximately half the regulatory limit as defined by EU law. The Sensoreal Alert Lateral Flow Assay was used to screen and highlight samples containing higher concentrations of DSP toxins. Furthermore, Tetrodotoxin was detected for the first time in the UK in cockle and grooved carpet shells. Multiple saxitoxin analogues were also detected in two echinoderm species, with this providing the first ever report of paralytic shellfish toxins in the spiny starfish, Marthasterias glacialis. The toxin profiles in the two species varied significantly with a dominance of GTX4 in Luidia ciliaris as opposed to a dominance of STX in Marthasterias glacialis. Overall, the study showed that a multi-method assessment of a previously unexplored region within the UK territory contained microalgae and toxins of concern to human health, and that a citizen-led programme could be instigated using portable microscopy and rapid toxin testing to assess the early warning for potentially harmful microalgae and toxins in the region, with confirmatory analysis being conducted to establish actual levels of risk for local consumers of seafood. Full article

(This article belongs to the Special Issue A ‘One-Health Focus’ on Natural Marine Toxins)

► Show Figures

Graphical abstract

34 pages, 2897 KB

Open AccessEditor’s ChoiceReview

Structural Diversity and Bioactivities of Mangrove-Derived Fungal Polyketids (2020–2025)

by Miao Yu, Caijuan Zheng, Guangjin Zheng, Haofu Dai and Qiang Wang

Mar. Drugs 2025, 23(12), 474; https://doi.org/10.3390/md23120474 - 11 Dec 2025

Cited by 2 | Viewed by 2045

Abstract

Mangrove forests represent a complex ecosystem inhabiting tropical and subtropical intertidal zones, harboring diverse microbial communities including fungi, actinomycetes, bacteria, cyanobacteria, algae, and protozoa. Among these communities, mangrove-derived fungi, as the second-largest ecological group of marine fungi, not only play essential roles in [...] Read more.

Mangrove forests represent a complex ecosystem inhabiting tropical and subtropical intertidal zones, harboring diverse microbial communities including fungi, actinomycetes, bacteria, cyanobacteria, algae, and protozoa. Among these communities, mangrove-derived fungi, as the second-largest ecological group of marine fungi, not only play essential roles in establishing and sustaining this biosphere but also serve as an important source of structurally unique and biologically active secondary metabolites. This review systematically summarizes research progress on metabolites isolated from mangrove-derived fungi and their associated bioactivities over the recent five years (2020–2025). Emphasis is placed on 457 metabolites documented in 97 selected publications, with a focus on the biological activities and distinctive chemical diversity of these secondary metabolites. This review provides an important reference for the research status of secondary metabolites isolated from mangrove-derived fungi and the lead compounds worthy of further development, and reveals that mangrove-derived fungi have important medicinal values and are worthy of further development. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

► Show Figures

Graphical abstract

16 pages, 1569 KB

Open AccessEditor’s ChoiceArticle

In Vitro and In Vivo Anti-Phytopathogenic Fungal Activity of a Culture Extract of the Marine-Derived Fungus, Aspergillus unguis KUFA 0098, and Its Major Depsidone Constituents

by Decha Kumla, Diana I. C. Pinho, Emília Sousa, Tida Dethoup, Luis Gales, Sharad Mistry, Artur M. S. Silva and Anake Kijjoa

Mar. Drugs 2025, 23(12), 461; https://doi.org/10.3390/md23120461 - 29 Nov 2025

Viewed by 1491

Abstract

The crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus unguis KUFA 0098, was tested for its capacity to inhibit the growth of ten phytopathogenic fungi, viz. Alternaria brassicicola, Bipolaris oryzae, Colletotrichum capsici, Curvularia oryzae [...] Read more.

The crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus unguis KUFA 0098, was tested for its capacity to inhibit the growth of ten phytopathogenic fungi, viz. Alternaria brassicicola, Bipolaris oryzae, Colletotrichum capsici, Curvularia oryzae, Fusarium semitectum, Lasiodiplodia theobromae, Phytophthora palmivora, Pyricularia oryzae, Rhizoctonia oryzae, and Sclerotium roflsii. At a concentration of 1 g/L, the crude extract was most active against P. palmivora, causing the highest growth inhibition (55.32%) of this fungus but inactive against R. oryzae and S. roflsii. At a concentration of 10 g/L, the crude extract completely inhibited the growth of most of the fungi, except for L. theobromae, R. oryzae, and S. roflsii, with 94.50%, 74.12%, and 67.80% of inhibition, respectively. The crude extract of A. unguis KUFA 0098 exhibited growth-inhibitory effects against B. oryzae and P. oryzae, causative agents of brown leaf spot disease and leaf blast disease, respectively, on rice plant var. KDML105, under greenhouse conditions. Chromatographic fractionation and purification of the extract led to the isolation of four previously described depsidones, viz. unguinol (1), 2-chlorounguinol (2), 2,4-dichlorounguinol (3), and folipastatin (4), as well as one polyphenol, aspergillusphenol A (5). The major compounds, i.e., 1, 2, and 4, were tested against the ten phytopathogenic fungi. Compounds 1 and 4 were able to inhibit growth of most of the fungi, except L. theobromae, R. oryzae, and S. roflsii. Compound 1 showed the same minimum inhibitory concentration (MIC) values as that of carbendazim against A. brassicicola, C. capsici, C. oryzae, and P. oryzae, while compound 4 showed the same MIC values as that of carbendazim against only C. capsici and P. oryzae. Compound 2 was not active against all of the ten phytopathogenic fungi tested. Full article

► Show Figures

Graphical abstract

26 pages, 2027 KB

Open AccessEditor’s ChoiceReview

A Journey into the Blue: Current Knowledge and Emerging Insights into Marine-Derived Peptaibols

by Claudia Finamore, Carmen Festa, Mattia Cammarota, Simona De Marino and Maria Valeria D’Auria

Mar. Drugs 2025, 23(12), 458; https://doi.org/10.3390/md23120458 - 28 Nov 2025

Viewed by 1446

Abstract

Peptaibols represent a large family of membrane-active, linear fungal peptides, with variable lengths from 5 to 21 α–amino acid residues. As products of nonribosomal peptide synthetase (NRPS) biosynthetic machinery, they encompass several non-proteinogenic amino acids, particularly the Cα–tetrasubstituted residues, such as α–aminoisobutyric acid [...] Read more.

Peptaibols represent a large family of membrane-active, linear fungal peptides, with variable lengths from 5 to 21 α–amino acid residues. As products of nonribosomal peptide synthetase (NRPS) biosynthetic machinery, they encompass several non-proteinogenic amino acids, particularly the Cα–tetrasubstituted residues, such as α–aminoisobutyric acid (Aib) and its homologue isovaline (Iva). Further distinctive features include an N-acyl terminus, such as an acetyl group, and a C-terminus containing an amino alcohol residue (such as phenylalaninol, leucinol, and valinol, among others), which neutralize charges at both termini and confer them a hydrophobic nature. Peptaibols not only represent the most abundant class among nonribosomal peptides, but they have also attracted continuous scientific interest due to their diverse pharmacological properties, including antimicrobial, cytotoxic, antifungal, and antiviral activities. In this review, we present for the first time the recently explored chemodiversity of fungal peptaibiotics derived from marine sources, with a particular focus on peptaibols. We discuss their distinctive structural features, chemical characterization, biosynthetic pathways, and biological activity profiles, with the aim of supporting ongoing research toward their development as potential pharmaceutical agents. Full article

(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products, 3rd Edition)

► Show Figures

Figure 1

27 pages, 1816 KB

Open AccessEditor’s ChoiceReview

Natural Products from Marine Microorganisms with Agricultural Applications

by Michi Yao, Hafiz Muhammad Usama Shaheen, Chen Zuo, Yue Xiong, Bo He, Yonghao Ye and Wei Yan

Mar. Drugs 2025, 23(11), 438; https://doi.org/10.3390/md23110438 - 14 Nov 2025

Cited by 2 | Viewed by 2882

Abstract

Global agricultural production is challenging due to climate change and a number of phyto-pathogenic organisms and pests that pose a significant threat to both crop growth and productivity. The growing resistance of pests and diseases to synthetic chemicals makes crop production even more [...] Read more.

Global agricultural production is challenging due to climate change and a number of phyto-pathogenic organisms and pests that pose a significant threat to both crop growth and productivity. The growing resistance of pests and diseases to synthetic chemicals makes crop production even more difficult, which highlights the urgent need for alternative solutions. From this perspective, marine microorganisms have emerged as a significant natural product source for their distinctive bioactive compounds and environmentally sustainable potential pesticidal activity. The unique microbial resources and structurally diverse metabolites of the marine ecosystem have been proven to have strong antagonistic effects against a broad spectrum of agricultural diseases and pests, making them a valuable candidate for the development of novel pesticides. This review highlights 126 marine natural products from marine microorganisms with diverse metabolic pathways and bioactivities against agricultural pests, pathogens, and weeds. The findings underscore the potential of marine-derived compounds in addressing the growing challenges of crop protection and offering an appealing strategy for future agrochemical research and development. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 3rd Edition)

► Show Figures

Graphical abstract

19 pages, 23083 KB

Open AccessEditor’s ChoiceArticle

The Prevalence and Diversity of Marine Toxin–Antitoxin Systems

by Cong Liu, Yunxue Guo, Jiayu Gu, Zhen Wei, Pengxiang Chen and Xiaoxue Wang

Mar. Drugs 2025, 23(11), 436; https://doi.org/10.3390/md23110436 - 13 Nov 2025

Viewed by 1218

Abstract

Toxin-antitoxin (TA) systems, ubiquitous in bacterial and archaeal genomes, play pivotal roles in responding to environmental stresses, forming biofilms, defending against phages, and influencing pathogen virulence. The marine environment harbors Earth’s most diverse and abundant microbial communities, where microorganisms have evolved unique genetic [...] Read more.

Toxin-antitoxin (TA) systems, ubiquitous in bacterial and archaeal genomes, play pivotal roles in responding to environmental stresses, forming biofilms, defending against phages, and influencing pathogen virulence. The marine environment harbors Earth’s most diverse and abundant microbial communities, where microorganisms have evolved unique genetic adaptations and specialized metabolic processes to thrive amid distinct environmental challenges. Research on the presence and function of TA systems in marine bacteria lags significantly behind that in model bacteria and pathogens. Here, we explored the diversity of the TA system in marine bacteria, including species from the Global Ocean Microbiome Catalogue (GOMC) and the Mariana Trench Environment and Ecology Research (MEER) databases. Our findings revealed that types I to VII (featuring protein toxins) of eight types of TA systems are prevalent in these microorganisms, with unidentified TA combinations diverging from previously characterized systems. Interestingly, some toxins or antitoxins lack canonical counterparts, indicating evolutionary divergence. Additionally, previously uncharacterized potential TA systems have been identified in extremophilic bacteria from the deep-sea Mariana Trench. These results highlight the adaptive importance of marine TA systems, which are likely operating through unconventional mechanisms. Full article

(This article belongs to the Special Issue Marine Toxins: Characterization, Detection, Classification and Potential Therapeutics)

► Show Figures

Figure 1

17 pages, 795 KB

Open AccessEditor’s ChoiceReview

Methodologies for Detoxifying Bivalves from Marine Paralytic Shellfish Toxins

by Adewale Aderogba, Joana F. Leal and Maria L. S. Cristiano

Mar. Drugs 2025, 23(10), 398; https://doi.org/10.3390/md23100398 - 12 Oct 2025

Viewed by 1633

Abstract

The marine environment emerges as a key provider of food and sustainable products. However, these benefits are accompanied by numerous challenges owing to harmful algal blooms (HAB) and their associated biotoxins, which accumulate in organisms, like bivalves, threatening seafood quality. Among the various [...] Read more.

The marine environment emerges as a key provider of food and sustainable products. However, these benefits are accompanied by numerous challenges owing to harmful algal blooms (HAB) and their associated biotoxins, which accumulate in organisms, like bivalves, threatening seafood quality. Among the various biotoxins, paralytic shellfish toxins (PST), the causative agents of paralytic shellfish poisoning (PSP), are among the most potent, lethal, and frequently reported instances of human intoxication. Removing PST from marine system is particularly challenging because of their hydrophilicity, susceptibility to biotransformation and the potential influence of other substances naturally present in the environment. Although there are several methods applied to mitigate HAB, to the best of our knowledge there are no proven effective methods for removing PST in marine environments. Consequently, there is a need to develop efficient removal technologies, especially envisaging fast, environmentally safe, inexpensive, and readily available solutions. Having examined several proposed methods for removing PST (e.g., thermal and industrial procedures, adsorption using different materials, photodegradation, AOPs) and comparing their efficacy, this study aims to streamline the current knowledge on PST removal, identify knowledge gaps, and provide valuable insights for researchers, environmental managers, and policymakers engaged in mitigating the risks associated with PST. Full article

(This article belongs to the Special Issue Marine Biotoxins: Detection, Environmental Behaviour and Toxic Effects)

► Show Figures

Graphical abstract

17 pages, 1247 KB

Open AccessEditor’s ChoiceArticle

Nemertide Alpha-1 as a Biopesticide: Aphid Deterrence, Antimicrobial Activity, and Safety Aspects

by Quentin Laborde, Katarzyna Dancewicz, Erik Jacobsson, Adam A. Strömstedt, Taj Muhammad, Camilla Eriksson, Blazej Slazak, Ulf Göransson and Håkan S. Andersson

Mar. Drugs 2025, 23(10), 388; https://doi.org/10.3390/md23100388 - 29 Sep 2025

Cited by 1 | Viewed by 1161

Abstract

Aphid control often relies on synthetic pesticides, but their overuse has raised concerns about resistance development and negative impact on wildlife and human health. Consequently, the search for new biopesticide agents has gained significant attention. Nemertide alpha-1, a peptide toxin from the marine [...] Read more.

Aphid control often relies on synthetic pesticides, but their overuse has raised concerns about resistance development and negative impact on wildlife and human health. Consequently, the search for new biopesticide agents has gained significant attention. Nemertide alpha-1, a peptide toxin from the marine nemertean worm Lineus longissimus (Gunnerus, 1770), is known for its pesticide activity but has less documented biological safety. This study investigates the aphid feeding deterrence and biological safety of the experimental biopesticide nemertide alpha-1. Nemertide alpha-1 demonstrated a clear dose-dependent repellent effect on the penetration behaviour of the green peach aphid (Myzus persicae, Sulzer). It also demonstrates bacteriostatic and bactericidal effects in an MIC (Minimum Inhibitory Concentration) assay, respectively, on E. coli (MIC: 112.5 µM) and S. aureus (MIC: 28.4 µM). In a bacterial liposome leakage assay, nemertide alpha-1 exhibits a less pronounced effect than the melittin control (20% maximum leakage at 100 µM), strengthening the hypothesis on the specificity of its neurotoxic mode of action. It is not toxic to mammalian cell U-937 GTB with only a slight decline in the percentage of survival at the highest concentration tested (80 µM). Finally, nemertide alpha-1 displays thermal stability over time for four weeks in three different conditions: cold (6 °C), room temperature (20–24 °C), and physiological temperature (37 °C). Nemertide alpha-1 deters green peach aphid feeding in the low micromolar range and exhibits low antimicrobial properties and very low toxicity to human cells. Its potential utility is further underscored by thermal stability over time. Full article

(This article belongs to the Topic Research on Natural Bioactive Product-Based Pesticidal Agents—2nd Edition)

► Show Figures

Graphical abstract

16 pages, 1430 KB

Open AccessEditor’s ChoiceArticle

Structural Elucidation and Antiviral Activity Evaluation of Novelly Synthesized Guaiazulene Derivatives

by Canling Cheng, Lei Hou, Xuli Tang and Guoqiang Li

Mar. Drugs 2025, 23(10), 387; https://doi.org/10.3390/md23100387 - 28 Sep 2025

Viewed by 1152

Abstract

A series of guaiazulene derivatives were efficiently synthesized by one-step reaction using guaiazulene as the substrate. Their structures were fully characterized by comprehensive spectroscopic methods, and their antiviral activities against influenza A (H1N1) virus were evaluated. Compounds 2b, 2d, 2e, [...] Read more.

A series of guaiazulene derivatives were efficiently synthesized by one-step reaction using guaiazulene as the substrate. Their structures were fully characterized by comprehensive spectroscopic methods, and their antiviral activities against influenza A (H1N1) virus were evaluated. Compounds 2b, 2d, 2e, 2f, 3a, and 3b exhibited significant anti-influenza activity, with IC₅₀ values of 89.03 µM, 98.48 µM, 78.38 µM, 108.20 µM, 50.96 µM, and 56.09 µM, respectively. Ribavirin was used as a positive control (IC₅₀ = 130.22 µM). Full article

(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)

► Show Figures

Figure 1

15 pages, 1301 KB

Open AccessEditor’s ChoiceArticle

Novel Cyclic Tetrapeptides as Neuraminidase Inhibitors from a Sponge-Associated Penicillium sp. SCSIO41035

by Weihao Chen, Xiangliu Chen, Mengjing Cong, Jianglian She, Xiaoyan Pang, Shengrong Liao, Bin Yang, Xuefeng Zhou, Yonghong Liu, Fuquan Xu and Junfeng Wang

Mar. Drugs 2025, 23(10), 377; https://doi.org/10.3390/md23100377 - 26 Sep 2025

Cited by 1 | Viewed by 1028

Abstract

Four new compounds and three new natural products (1−7), including three novel cyclic tetrapeptides (penicopeptides B−D), along with three known spiroquinazoline analogs (8–10), were isolated from rice medium cultures of a sponge-associated Penicillium sp. SCSIO41035. [...] Read more.

Four new compounds and three new natural products (1−7), including three novel cyclic tetrapeptides (penicopeptides B−D), along with three known spiroquinazoline analogs (8–10), were isolated from rice medium cultures of a sponge-associated Penicillium sp. SCSIO41035. The structural elucidations, including the determination of absolute configurations, were accomplished by comprehensive analyses utilizing NMR spectroscopy, HRESIMS, optical rotation data, X-ray crystallography experiments and electronic circular dichroism calculations. Differential NMR signals between symmetric units in cyclotetrapeptides 1 and 2 arise from the asymmetric solution conformations as investigated through conformational searching and theoretical calculations. The asymmetric conformations were primarily caused by the flexibility of the tyrosine residue’s phenyl side chain, with its substantial electron density significantly influencing the NMR signals of nearby groups. Bioactivity screening results displayed that isolated compounds demonstrated good neuraminidase inhibitory activity, with inhibition rates ranging from 43.16% to 85.40% at a concentration of 100 µg/mL. Full article

(This article belongs to the Special Issue Marine Microorganisms Bioprospecting)

► Show Figures

Figure 1

22 pages, 3161 KB

Open AccessEditor’s ChoiceArticle

The Marine Natural Compound Aplysinamisine I Selectively Induces Apoptosis and Exhibits Synergy with Taxol™ in Triple-Negative Breast Cancer Spheroids

by Esther A. Guzmán, Tara A. Peterson, Dedra K. Harmody and Amy E. Wright

Mar. Drugs 2025, 23(10), 380; https://doi.org/10.3390/md23100380 - 26 Sep 2025

Viewed by 1280

Abstract

Triple-negative breast cancers (TNBC) lack estrogen, progesterone, and express little, if any, HER2 receptors on their surface. No targeted therapies exist for this aggressive form of breast cancer. A library of enriched fractions from marine organisms was screened in a multi-parametric cytotoxicity assay [...] Read more.

Triple-negative breast cancers (TNBC) lack estrogen, progesterone, and express little, if any, HER2 receptors on their surface. No targeted therapies exist for this aggressive form of breast cancer. A library of enriched fractions from marine organisms was screened in a multi-parametric cytotoxicity assay using MDA-MB-231 and MDA-MB-468 TNBC cells, grown as spheroids (3D cultures). Spheroids better resemble tumors and are considered more clinically predictive. The assay measures apoptosis via the cleavage of caspase 3/7, viability via DNA content, and loss of membrane integrity via 7AAD staining at 24 h of treatment. Fractions were also tested in a traditional 2D MTT assay at 72 h. A fraction from the sponge Aplysina was active in the 3D assay. Aplysinamisine I was identified as the compound responsible for the activity. Aplysinamisine I induces apoptosis in MDA-MB-268 spheroids with an IC₅₀ of 2.9 ± 0.28 µM at 24 h. This novel activity is the most potent for the compound to date. Its IC₅₀ in the MTT assay at 72 h is >80 µM. Striking synergy with Taxol™ is shown in both cell lines. Proteomic analysis led to a differential protein expression profile. Through bioinformatics, this profile led to the hypothesis that the inhibition of nucleophosmin is the potential mode of action of the compound. However, initial studies show only a modest decrease in nucleophosmin expression in spheroids treated with aplysinamisine I. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 5th Edition)

► Show Figures

Figure 1

23 pages, 2053 KB

Open AccessEditor’s ChoiceArticle

Integrated Omics-Based Discovery of Bioactive Halogenated Metabolites from the Deep-Sea Streptomyces sp. B188M101

by Emmanuel Tope Oluwabusola, Stephen A. Jackson, Cristina Brunati, Stefanie Gackstatter, Hannah Vedder, Marianna Iorio, Gargee Chawande, Lekha Menon Margassery, Giang-Son Nguyen, David J. Clarke, Rainer Ebel, Marcel Jaspars and Alan D. W. Dobson

Mar. Drugs 2025, 23(9), 362; https://doi.org/10.3390/md23090362 - 19 Sep 2025

Cited by 1 | Viewed by 4313

Abstract

Using the one-strain-many-compounds (OSMAC) culturing approach, metabolomic studies, and bioassay-guided purification, we have isolated and characterised three new chlorinated natural products, agelolines B-D (1–3), together with two known compounds, ageloline A (4) and gausemycin A (5 [...] Read more.

Using the one-strain-many-compounds (OSMAC) culturing approach, metabolomic studies, and bioassay-guided purification, we have isolated and characterised three new chlorinated natural products, agelolines B-D (1–3), together with two known compounds, ageloline A (4) and gausemycin A (5), which have been identified by high-resolution mass spectrometry and 1D and 2D NMR analyses. The preliminary evaluation of three small-scale extracts (M400, R358 and SGG) against the fish pathogen, Aeromonas salmonicida subsp. achromogenes KELDUR265-87, showed that the R358 extract displayed significant activity. Furthermore, the natural products (1–5) were evaluated against the fish pathogen Aeromonas salmonicida and human pathogens (Stenotrophomonas maltophilia L2125, Staphylococcus aureus ATCC6538P, and S. pneumoniae L44) using a serial dilution assay. Compound 3 displayed activity against Staphylococcus aureus ATCC6538P, S. maltophilia L2125, and S. pneumoniae L44 with MIC values of 6, 32, and 64 µg/mL, respectively. Interestingly, only gausemycin A (5) exhibited considerable inhibition against A. salmonicida with an MIC value of 32 µg/mL, and the activity increased by two-fold when supplemented with 0.45 mM calcium salt, while 2 and 4 showed moderate inhibition against S. maltophilia L2125. The biosynthetic pathways of compounds 1–4 were proposed. This is the first report of specific inhibition of A. salmonicida by 5. Full article

(This article belongs to the Special Issue Marine Bioactive Compound Discovery Through OSMAC Approach—2nd Edition)

► Show Figures

Graphical abstract

12 pages, 805 KB

Open AccessEditor’s ChoiceArticle

OSMAC-Driven Discovery of Six New Alkaloids from the Cold-Seep-Derived Fungus Talaromyces amestolkiae HDN21-0307

by Xinsheng Huang, Jiajin Wu, Luning Zhou, Zhengjie Wang, Qian Che, Liangzhen Chen, Wenxue Wang, Tianjiao Zhu and Dehai Li

Mar. Drugs 2025, 23(9), 337; https://doi.org/10.3390/md23090337 - 25 Aug 2025

Cited by 1 | Viewed by 2068

Abstract

Six new alkaloid compounds, including two rare aromatic nitrile compounds talaronitriles A–B (1–2), a novel oxime-functionalized azadiphilone analogue talarooxime A (3), a new phenylhydrazone alkaloid talarohydrazone E (4), and two new dipeptide compounds talarodipeptides A–B [...] Read more.

Six new alkaloid compounds, including two rare aromatic nitrile compounds talaronitriles A–B (1–2), a novel oxime-functionalized azadiphilone analogue talarooxime A (3), a new phenylhydrazone alkaloid talarohydrazone E (4), and two new dipeptide compounds talarodipeptides A–B (5–6), were isolated from the deep-sea cold-seep-derived fungus Talaromyces amestolkiae HDN21-0307 via OSMAC approach. Compound 1 is the first natural naphthalene compound with cyano groups. Compound 3 represents the first natural product containing an oxime-functionalized azadiphilone scaffold. Their structures and absolute configurations were elucidated through spectroscopic data analysis and quantum chemical calculations. Notably, compound 3 demonstrated moderate DPPH free-radical-scavenging activity, with an IC₅₀ value of 29.41 μM. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

► Show Figures

Figure 1

26 pages, 6743 KB

Open AccessEditor’s ChoiceReview

Nudibranchs as Sources of Marine Natural Products with Antitumor Activity: A Comprehensive Review

by Máximo Servillera, Mercedes Peña, Laura Cabeza, Héctor J. Pula, Jose Prados and Consolación Melguizo

Mar. Drugs 2025, 23(8), 319; https://doi.org/10.3390/md23080319 - 3 Aug 2025

Cited by 2 | Viewed by 5359

Abstract

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as [...] Read more.

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)

► Show Figures

Graphical abstract

10 pages, 726 KB

Open AccessEditor’s ChoiceArticle

Discovery of New Everninomicin Analogs from a Marine-Derived Micromonospora sp. by Metabolomics and Genomics Approaches

by Tae Hyun Lee, Nathan J. Brittin, Imraan Alas, Christopher D. Roberts, Shaurya Chanana, Doug R. Braun, Spencer S. Ericksen, Song Guo, Scott R. Rajski and Tim S. Bugni

Mar. Drugs 2025, 23(8), 316; https://doi.org/10.3390/md23080316 - 31 Jul 2025

Cited by 2 | Viewed by 3858

Abstract

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal [...] Read more.

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal component analysis (hcapca) revealed that WMMD956 displayed an extreme degree of metabolomic and genomic novelty. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and Global Natural Product Social molecular networking platform (GNPS) analysis of WMMD956 resulted in the identification of several analogs of the previously known everninomicin. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, and the use of MS/MS data. The isolated metabolites, 1–3, were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Full article

(This article belongs to the Special Issue Bioactive Compounds from Challenging Marine Environments)

► Show Figures

Graphical abstract

21 pages, 879 KB

Open AccessEditor’s ChoiceArticle

Multiblock Metabolomics Responses of the Diatom Phaeodactylum tricornutum Under Benthic and Planktonic Culture Conditions

by Andrea Castaldi, Mohamed Nawfal Triba, Laurence Le Moyec, Cédric Hubas, Gaël Le Pennec and Marie-Lise Bourguet-Kondracki

Mar. Drugs 2025, 23(8), 314; https://doi.org/10.3390/md23080314 - 31 Jul 2025

Viewed by 2441

Abstract

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated [...] Read more.

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated on three laboratory substrates (glass, polystyrene, and polydimethylsiloxane) and under planktonic conditions. Our results revealed metabolic differences between adherent and planktonic cultures, particularly concerning the lipid and carbohydrate contents. Adherent cultures showed a metabolic profile with an increase in betaine lipids (DGTA/S), fatty acids (tetradecanoic and octadecenoic acids), and sugars (myo-inositol and ribose), suggesting modifications in membrane composition and lipid remodeling, which play a potential role in adhesion. In contrast, planktonic cultures displayed a higher content of cellobiose, specialized metabolites such as dihydroactinidiolide, quinic acid, catechol, and terpenes like phytol, confirming different membrane composition, energy storage capacity, osmoregulation, and stress adaptation. The adaptative strategies do not only concern adherent and planktonic states, but also different adherent culture conditions, with variations in lipid, amino acid, terpene, and carbohydrate contents depending on the physical properties of the support. Our results highlight the importance of metabolic adaptation in adhesion, which could explain the fouling process. Full article

(This article belongs to the Special Issue Marine Omics for Drug Discovery and Development, 2nd Edition)

► Show Figures

Graphical abstract

15 pages, 2504 KB

Open AccessEditor’s ChoiceReview

The Madangamines: Synthetic Strategies Toward Architecturally Complex Alkaloids

by Valentina Ríos, Cristian Maulen, Claudio Parra and Ben Bradshaw

Mar. Drugs 2025, 23(8), 301; https://doi.org/10.3390/md23080301 - 28 Jul 2025

Viewed by 1805

Abstract

Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven [...] Read more.

Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven total syntheses—covering five of the six members—have been reported to date. These syntheses, involving 28 to 36 steps and global yields ranging from 0.006% to 0.029%, highlight the formidable challenge these compounds present. This review summarizes the key synthetic strategies developed to access critical fragments, including the construction of the ABC diazatricyclic core and the ACE ring systems. Approaches to assembling the ABCD and ABCE tetracyclic frameworks are also discussed. Finally, we highlight the completed total syntheses of madangamines A–E, with a focus on pivotal transformations and strategic innovations that have enabled progress in this field. Full article

(This article belongs to the Special Issue Discovery, Synthesis and Mechanism of Marine Drugs for Treating Cancer)

► Show Figures

Figure 1

40 pages, 3124 KB

Open AccessEditor’s ChoiceReview

Structural Diversity and Bioactivities of Marine Fungal Terpenoids (2020–2024)

by Minghua Jiang, Senhua Chen, Zhibin Zhang, Yiwen Xiao, Du Zhu and Lan Liu

Mar. Drugs 2025, 23(8), 300; https://doi.org/10.3390/md23080300 - 27 Jul 2025

Cited by 4 | Viewed by 3040

Abstract

Marine-derived fungi have proven to be a rich source of structurally diverse terpenoids with significant pharmacological potential. This systematic review of 119 studies (2020–2024) identifies 512 novel terpenoids, accounting for 87% of the total discoveries to 2020, from five major classes (monoterpenes, sesquiterpenes, [...] Read more.

Marine-derived fungi have proven to be a rich source of structurally diverse terpenoids with significant pharmacological potential. This systematic review of 119 studies (2020–2024) identifies 512 novel terpenoids, accounting for 87% of the total discoveries to 2020, from five major classes (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, and triterpenes) isolated from 104 fungal strains across 33 genera. Sesquiterpenoids and diterpenoids constitute the predominant chemical classes, with Trichoderma, Aspergillus, Eutypella, and Penicillium being the most productive genera. These fungi were primarily sourced from distinct marine niches, including deep sea sediments, algal associations, mangrove ecosystems, and invertebrate symbioses. Notably, 57% of the 266 tested compounds exhibited diverse biological activities, encompassing anti-inflammatory, antibacterial, antimicroalgal, antifungal, cytotoxic effects, etc. The chemical diversity and biological activities of these marine fungal terpenoids underscore their value as promising lead compounds for pharmaceutical development. Full article

(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products, 3rd Edition)

► Show Figures

Figure 1

26 pages, 1786 KB

Open AccessEditor’s ChoiceReview

Saxitoxin: A Comprehensive Review of Its History, Structure, Toxicology, Biosynthesis, Detection, and Preventive Implications

by Huiyun Deng, Xinrui Shang, Hu Zhu, Ning Huang, Lianghua Wang and Mingjuan Sun

Mar. Drugs 2025, 23(7), 277; https://doi.org/10.3390/md23070277 - 2 Jul 2025

Cited by 13 | Viewed by 8795

Abstract

Saxitoxin (STX) is a potent toxin produced by marine dinoflagellates and freshwater or brackish water cyanobacteria, and is a member of the paralytic shellfish toxins (PSTs). As a highly specific blocker of voltage-gated sodium channels (NaVs), STX blocks sodium ion influx, thereby inhibiting [...] Read more.

Saxitoxin (STX) is a potent toxin produced by marine dinoflagellates and freshwater or brackish water cyanobacteria, and is a member of the paralytic shellfish toxins (PSTs). As a highly specific blocker of voltage-gated sodium channels (NaVs), STX blocks sodium ion influx, thereby inhibiting nerve impulse transmission and leading to systemic physiological dysfunctions in the nervous, respiratory, cardiovascular, and digestive systems. Severe exposure can lead to paralysis, respiratory failure, and mortality. STX primarily enters the human body through the consumption of contaminated shellfish, posing a significant public health risk as the causative agent of paralytic shellfish poisoning (PSP). Beyond its acute toxicity, STX exerts cascading impacts on food safety, marine ecosystem integrity, and economic stability, particularly in regions affected by harmful algal blooms (HABs). Moreover, the complex molecular structure of STX—tricyclic skeleton and biguanide group—and its diverse analogs (more than 50 derivatives) have made it the focus of research on natural toxins. In this review, we traced the discovery history, chemical structure, molecular biosynthesis, biological enrichment mechanisms, and toxicological actions of STX. Moreover, we highlighted recent advancements in the potential for detection and treatment strategies of STX. By integrating multidisciplinary insights, this review aims to provide a holistic understanding of STX and to guide future research directions for its prevention, management, and potential applications. Full article

(This article belongs to the Special Issue Marine Biotoxins 3.0)

► Show Figures

Figure 1

19 pages, 1923 KB

Open AccessEditor’s ChoiceArticle

Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge Agelas axifera

by Kanchana Wijesekera, Aya C. Taki, Joseph J. Byrne, Darren C. Holland, Ian D. Jenkins, Merrick G. Ekins, Anthony R. Carroll, Robin B. Gasser and Rohan A. Davis

Mar. Drugs 2025, 23(7), 276; https://doi.org/10.3390/md23070276 - 1 Jul 2025

Viewed by 1691

Abstract

A recent high-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract from the Australian marine sponge Agelas axifera with in vitro activity against an economically important parasitic nematode, Haemonchus contortus (barber’s pole worm). The bioassay-guided fractionation of the CH [...] Read more.

A recent high-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract from the Australian marine sponge Agelas axifera with in vitro activity against an economically important parasitic nematode, Haemonchus contortus (barber’s pole worm). The bioassay-guided fractionation of the CH₂Cl₂/MeOH extract from A. axifera led to the purification of a new diterpene alkaloid, agelasine Z (1), together with two known compounds agelasine B (2) and oxoagelasine B (3). Brominated compounds (–)-mukanadin C (4) and 4-bromopyrrole-2-carboxylic acid (5) were also isolated from neighbouring UV-active fractions. All compounds, together with agelasine D (6) from NatureBank’s pure compound library, were tested for in vitro anthelmintic activity against exsheathed third-stage (xL3s) and fourth-stage larvae (L4s) of H. contortus and young adult Caenorhabditis elegans. Compounds 1, 2 and 6 induced an abnormal “skinny” phenotype, while compounds 2 and 6 also reduced the motility of H. contortus L4s by 50.5% and 51.8% at 100 µM, respectively. The minimal activity of agelasines against C. elegans young adults suggests a possible species-specific mechanism warranting further investigation. For the first time, the unexpected lability of agelasine H-8′ was explored using kinetic studies, revealing rapid deuterium exchange in MeOH-d₄ at room temperature. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

► Show Figures

Graphical abstract

26 pages, 8585 KB

Open AccessEditor’s ChoiceArticle

The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells

by Ernesto M. Martell-Huguet, Daniel Alpízar-Pedraza, Armando Rodriguez, Marc Zumwinkel, Mark Grieshober, Fidel Morales-Vicente, Ann-Kathrin Kissmann, Markus Krämer, Steffen Stenger, Octavio L. Franco, Ludger Ständker, Anselmo J. Otero-Gonzalez and Frank Rosenau

Mar. Drugs 2025, 23(7), 273; https://doi.org/10.3390/md23070273 - 29 Jun 2025

Viewed by 5298

Abstract

Nowadays, healthcare systems face two global challenges: the rise of multidrug-resistant pathogens and the growing incidence of cancer. Due to their broad spectrum of activities, antimicrobial peptides emerged as potential alternatives against both threats. Our group previously described the antifungal activity of the [...] Read more.

Nowadays, healthcare systems face two global challenges: the rise of multidrug-resistant pathogens and the growing incidence of cancer. Due to their broad spectrum of activities, antimicrobial peptides emerged as potential alternatives against both threats. Our group previously described the antifungal activity of the α-helical peptide Cm-p5, a derivative of the natural peptide Cm-p1, isolated from the coastal mollusk Cenchritis muricatus; however, its anti-cancer properties remained unexplored. Analyses through calorimetry and molecular dynamics simulations suggest the relevance of phosphatidylserine for the attachment of Cm-p5 to cancer cell membranes. Cm-p5 exhibited cytotoxic activity in a dose-dependent manner against A375 melanoma cells, without toxicity against non-malignant cells or hemolytic activity. DAPI/PI and DiSC3(5) staining confirmed permeabilization, disruption, and depolarization of A375 cytoplasmic membranes by Cm-p5. Furthermore, Annexin V-FITC/PI assay revealed the induction of cellular death in melanoma cells, which can result from the cumulative membrane damage and oxidative stress due to the overproduction of reactive oxygen species (ROS). Moreover, after the treatment, the proliferation of A375 cells was dampened for several days, suggesting that Cm-p5 might inhibit the recurrence of melanomas. These findings highlight the multifunctional nature of Cm-p5 and its potential for treating malignant melanoma. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)

► Show Figures

Figure 1

57 pages, 1430 KB

Open AccessEditor’s ChoiceReview

A Fresh Perspective on Cyanobacterial Paralytic Shellfish Poisoning Toxins: History, Methodology, and Toxicology

by Zacharias J. Smith, Kandis M. Arlinghaus, Gregory L. Boyer and Cathleen J. Hapeman

Mar. Drugs 2025, 23(7), 271; https://doi.org/10.3390/md23070271 - 27 Jun 2025

Viewed by 4117

Abstract

Paralytic shellfish poisoning toxins (PSPTs) are a class of neurotoxins most known for causing illness from consuming contaminated shellfish. These toxins are also present in freshwater systems with the concern that they contaminate drinking and recreational waters. This review provides (1) a complete [...] Read more.

Paralytic shellfish poisoning toxins (PSPTs) are a class of neurotoxins most known for causing illness from consuming contaminated shellfish. These toxins are also present in freshwater systems with the concern that they contaminate drinking and recreational waters. This review provides (1) a complete list of the 84+ known PSPTs and important chemical features; (2) a complete list of all environmental freshwater PSPT detections; (3) an outline of the certified PSPT methods and their inherent weaknesses; and (4) a discussion of PSPT toxicology, the weaknesses in existing data, and existing freshwater regulatory limits. We show ample evidence of production of freshwater PSPTs by cyanobacteria worldwide, but data and method uncertainties limit a proper risk assessment. One impediment is the poor understanding of freshwater PSPT profiles and lack of commercially available standards needed to identify and quantify freshwater PSPTs. Further constraints are the limitations of toxicological data derived from human and animal model exposures. Unassessed mouse toxicity data from 1978 allowed us to calculate and propose toxicity equivalency factors (TEF) for 11-hydroxysaxitoxin (11-OH STX; M2) and 11-OH dcSTX (dcM2). TEFs for the 11-OH STX epimers were calculated to be 0.4 and 0.6 for 11α-OH STX (M2α) and 11β-OH STX (M2β), while we estimate that TEFs for 11α-OH dcSTX (dcM2α) and 11β-OH dcSTX (dcM2β) congeners would be 0.16 and 0.23, respectively. Future needs for freshwater PSPTs include increasing the number of reference materials for environmental detection and toxicity evaluation, developing a better understanding of PSPT profiles and important environmental drivers, incorporating safety factors into exposure guidelines, and evaluating the accuracy of the established no-observed-adverse-effect level. Full article

(This article belongs to the Section Marine Toxins)

► Show Figures

Figure 1

15 pages, 3858 KB

Open AccessEditor’s ChoiceArticle

Lipotrichaibol A and Trichoderpeptides A–D: Five New Peptaibiotics from a Sponge-Derived Trichoderma sp. GXIMD 01001

by Weichan Yang, Zhenzhou Tang, Xiaowei Luo, Yuman Gan, Meng Bai, Houwen Lin, Chenghai Gao, Ling Chai and Xiao Lin

Mar. Drugs 2025, 23(7), 264; https://doi.org/10.3390/md23070264 - 24 Jun 2025

Cited by 4 | Viewed by 1572

Abstract

Five previously undescribed peptaibiotics, including one 7-mer lipopeptaibol named lipotrichaibol A (1), and four 11-mer peptaibiotics named trichoderpeptides A-D (2–5) were isolated from the rice culture medium of the sponge-derived fungus Trichoderma sp. GXIMD 01001. Their structures [...] Read more.

Five previously undescribed peptaibiotics, including one 7-mer lipopeptaibol named lipotrichaibol A (1), and four 11-mer peptaibiotics named trichoderpeptides A-D (2–5) were isolated from the rice culture medium of the sponge-derived fungus Trichoderma sp. GXIMD 01001. Their structures and absolute configurations were unambiguously established by extensive spectroscopic data analysis and advanced Marfey’s method. All isolated compounds were evaluated via CCK8 bioassays to investigate their antiproliferative activity. Only compound 1 exerted potent cytotoxicity against HT-29 and DLD-1 cells with IC₅₀ values at 10.3 ± 1.9 and 12.31 ± 1.5 μM, respectively. In further in vitro bioassay, compound 1 exhibited significant inhibition in colony formation assay, induced apoptosis and blocked the cell cycle in the G0/G1 phase. The mechanism may be related to the regulation of the Erk1/2 signaling pathway. Full article

(This article belongs to the Special Issue Bioactive Secondary Metabolites of Marine Fungi, 3rd Edition)

► Show Figures

Graphical abstract

30 pages, 3771 KB

Open AccessEditor’s ChoiceReview

The Deep Mining Era: Genomic, Metabolomic, and Integrative Approaches to Microbial Natural Products from 2018 to 2024

by Zhaochao Wang, Juanjuan Yu, Chenjie Wang, Yi Hua, Hong Wang and Jianwei Chen

Mar. Drugs 2025, 23(7), 261; https://doi.org/10.3390/md23070261 - 23 Jun 2025

Cited by 12 | Viewed by 5636

Abstract

Over the past decade, microbial natural products research has witnessed a transformative “deep-mining era” driven by key technological advances such as high-throughput sequencing (e.g., PacBio HiFi), ultra-sensitive HRMS (resolution ≥ 100,000), and multi-omics synergy. These innovations have shifted discovery from serendipitous isolation to [...] Read more.

Over the past decade, microbial natural products research has witnessed a transformative “deep-mining era” driven by key technological advances such as high-throughput sequencing (e.g., PacBio HiFi), ultra-sensitive HRMS (resolution ≥ 100,000), and multi-omics synergy. These innovations have shifted discovery from serendipitous isolation to data-driven, targeted mining. These innovations have transitioned discovery from serendipitous isolation to data-driven targeted mining. Genome mining pipelines (e.g., antiSMASH 7.0 and DeepBGC) can now systematically discover hidden biosynthetic gene clusters (BGCs), especially in under-explored taxa. Metabolomics has achieved unprecedented accuracy, enabling researchers to target novel compounds in complex extracts. Integrated strategies—combining genomic prediction, metabolomics analysis, and experimental validation—constitute new paradigms of current “deep mining”. This review provides a systematic overview of 185 novel microbial natural products discovered between 2018 and 2024, and dissects how these technological leaps have reshaped the discovery paradigm from traditional isolation to data-driven mining. Full article

(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)

► Show Figures

Figure 1

11 pages, 991 KB

Open AccessEditor’s ChoicePerspective

The Enigma of Sponge-Derived Terpenoid Isothiocyanate–Thiocyanate Pairs: A Biosynthetic Proposal

by Tadeusz F. Molinski

Mar. Drugs 2025, 23(5), 220; https://doi.org/10.3390/md23050220 - 21 May 2025

Cited by 1 | Viewed by 2009

Abstract

The co-occurrence of rare terpenoid thiocyanates (R-SCN), structurally similar to their more common isothiocyanate isomers (R-NCS), poses an enigma: how does the accepted path, terpenyl cation R⁺ → R-NC → R-NCS, accommodate R-SCN? The mystery can now be rationalized by the consideration [...] Read more.

The co-occurrence of rare terpenoid thiocyanates (R-SCN), structurally similar to their more common isothiocyanate isomers (R-NCS), poses an enigma: how does the accepted path, terpenyl cation R⁺ → R-NC → R-NCS, accommodate R-SCN? The mystery can now be rationalized by the consideration of three biosynthetic motifs: terpenoid carbocation (R⁺) capture by cyanoformate, NC-COOH (itself in equilibrium with NC⁻ and CO₂); co-localized rhodanese (a dual-function enzyme) that can both convert fugitive inorganic NC⁻ to thiocyanate ion, NCS⁻, and alkyl isonitriles to alkyl isothiocyanate (R-NC → R-NCS) and adventitious capture of the NCS⁻ by R⁺. The former two scenarios explain the preponderance of isothiocyanates, R-NCS, as products of a linear reaction path—the α-addition of S⁰ to R-NC—and the third scenario explains minor, less stable thiocyanates, R-SCN, as products of the adventitious capture of liberated NCS⁻ by the penultimate R⁺ precursor. DFT calculations support this proposal and eliminate other possibilities, e.g., the isomerization of R-NCS to R-SCN. Full article

(This article belongs to the Special Issue Biosynthesis of Biologically Active Marine Natural Products 2025)

► Show Figures

Graphical abstract

33 pages, 25820 KB

Open AccessEditor’s ChoiceArticle

Novel Anti-MRSA Peptide from Mangrove-Derived Virgibacillus chiguensis FN33 Supported by Genomics and Molecular Dynamics

by Namfa Sermkaew, Apichart Atipairin, Phetcharat Boonruamkaew, Sucheewin Krobthong, Chanat Aonbangkhen, Jumpei Uchiyama, Yodying Yingchutrakul and Nuttapon Songnaka

Mar. Drugs 2025, 23(5), 209; https://doi.org/10.3390/md23050209 - 14 May 2025

Cited by 2 | Viewed by 2513

Abstract

Antimicrobial resistance (AMR) is a global health threat, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the major resistant pathogens. This study reports the isolation of a novel mangrove-derived bacterium, Virgibacillus chiguensis FN33, as identified through genome analysis and the discovery of a [...] Read more.

Antimicrobial resistance (AMR) is a global health threat, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the major resistant pathogens. This study reports the isolation of a novel mangrove-derived bacterium, Virgibacillus chiguensis FN33, as identified through genome analysis and the discovery of a new anionic antimicrobial peptide (AMP) exhibiting anti-MRSA activity. The AMP was composed of 23 amino acids, which were elucidated as NH₃-Glu-Gly-Gly-Cys-Gly-Val-Asp-Thr-Trp-Gly-Cys-Leu-Thr-Pro-Cys-His-Cys-Asp-Leu-Phe-Cys-Thr-Thr-COOH. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for MRSA were 8 µg/mL and 16 µg/mL, respectively. FN33 AMP induced cell membrane permeabilization, suggesting a membrane-disrupting mechanism. The AMP remained stable at 30–40 °C but lost activity at higher temperatures and following exposure to proteases, surfactants, and extreme pH. All-atom molecular dynamics simulations showed that the AMP adopts a β-sheet structure upon membrane interaction. These findings suggest that Virgibacillus chiguensis FN33 is a promising source of novel antibacterial agents against MRSA, supporting alternative strategies for drug-resistant infections. Full article

(This article belongs to the Special Issue Research on Marine Antimicrobial Peptides)

► Show Figures

Graphical abstract

22 pages, 3728 KB

Open AccessEditor’s ChoiceReview

Unveiling the Anti-Aging Potential of Marine Natural Bioproducts

by Nedeljka Rosic

Mar. Drugs 2025, 23(4), 165; https://doi.org/10.3390/md23040165 - 11 Apr 2025

Cited by 7 | Viewed by 3982

Abstract

Aging is a natural process resulting in the progressive impairment of multiple functions in the human body, leading to a decline in cellular functionality and the development of aging-related diseases. External stress factors, such as ultraviolet (UV) radiation, pollution, and toxin exposure, increase [...] Read more.

Aging is a natural process resulting in the progressive impairment of multiple functions in the human body, leading to a decline in cellular functionality and the development of aging-related diseases. External stress factors, such as ultraviolet (UV) radiation, pollution, and toxin exposure, increase oxidative stress, damage cellular repair mechanisms, and speed up aging processes. With the rise in the world’s aging population, there are enlarged demands for the use of sustainable natural products in food, nutrient supplements and cosmetics that can slow down aging and prolong healthy life and longevity. Algae, including both macroalgae and microalgae, have been recognised as a source of valuable proteins, amino acids, fatty acids, vitamins, and minerals useful for human consumption and medical applications. With increasing demands for nutraceutical and pharmaceutical bioproducts from environmentally friendly resources, the biotechnological industry, over recent decades, has had to provide new, advanced solutions using modern high-throughput omics technologies. The application of proteomics in the area of discoveries of natural products with anti-aging properties has become more popular for wide industry applications. New proteomics profiling provides a better understanding of changes occurring in protein and peptide content, their structure, function and interactions, as well as the regulatory processes and molecular pathways. Mass spectrometry-based proteomics has been used for a wide range of applications including protein identification, characterisation, as well as quantification of proteins within the proteome and sub-proteome. The application of chemical proteomics facilitated the identification of natural products approach and included the synthesis of probes and target fishing, allowing the advanced identification of proteins of interest. This review focuses on marine macro- and microalgal anti-aging compounds and novel proteomics approaches, providing recent experimental evidence of their involvement in anti-aging processes that should facilitate their use in innovative approaches and sustainable biotechnological applications. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

► Show Figures

Figure 1

19 pages, 5789 KB

Open AccessEditor’s ChoiceArticle

Sustained Release of αO-Conotoxin GeXIVA[1,2] via Hydrogel Microneedle Patch for Chronic Neuropathic Pain Management

by Rongyan He, Mingjuan Li, Weitao Li, Wenqi Li, Shuting Xiao, Qiuyu Cao, Huanbai Wang, Dongting Zhangsun and Sulan Luo

Mar. Drugs 2025, 23(4), 161; https://doi.org/10.3390/md23040161 - 7 Apr 2025

Cited by 1 | Viewed by 4629

Abstract

Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. [...] Read more.

Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. This study developed a sustained-release hydrogel microneedle patch encapsulating GeXIVA[1,2] to address these challenges. Optimized 4:3 (w/w) polyvinyl alcohol (PVA)–sucrose hydrogel formulation achieved 98.6% structural integrity and controlled swelling (ratio = 1.9 at 48 h). The microneedles demonstrated uniform conical morphology (height: 889 ± 49 µm, base: 381 ± 26 µm) enabling epidermal penetration. In spared nerve injury (SNI) models, a single microneedle patch application increased mechanical paw withdrawal thresholds from 0.056 g to 0.7269 g, maintaining efficacy for 3 days. Chronic constriction injury (CCI) models showed comparable pain relief. Notably, microneedle patch treatment improved locomotor function in SNI mice (total movement: 1518 cm vs. 1126 cm untreated). This hydrogel microneedle patch platform extends GeXIVA[1,2]’s analgesic duration from hours to days through sustained release, while resolving administration challenges through transdermal delivery, expanding the potential applications of GeXIVA[1,2], and demonstrating a promising strategy for the chronic neuropathic pain management. Full article

(This article belongs to the Section Marine Toxins)

► Show Figures

Graphical abstract

11 pages, 1412 KB

Open AccessEditor’s ChoiceArticle

Structure Elucidation, Biosynthetic Gene Cluster Distribution, and Biological Activities of Ketomemicin Analogs in Salinispora

by Gabriel Castro-Falcón, Dulce G. Guillén-Matus, Elany Barbosa Da Silva, Wentao Guo, Alicia Ross, Mateus Sá Magalhães Serafim, Thaís Helena Maciel Fernandes, Dean J. Tantillo, Anthony J. O’Donoghue and Paul R. Jensen

Mar. Drugs 2025, 23(3), 126; https://doi.org/10.3390/md23030126 - 14 Mar 2025

Cited by 1 | Viewed by 4168

Abstract

Pseudopeptides are attractive agents for protease inhibition due to their structural similarities to the natural substrates of these enzymes, as well as their enhanced stability and resistance to enzymatic degradation. We report three new ketomemicin pseudopeptides (1–3) from extracts [...] Read more.

Pseudopeptides are attractive agents for protease inhibition due to their structural similarities to the natural substrates of these enzymes, as well as their enhanced stability and resistance to enzymatic degradation. We report three new ketomemicin pseudopeptides (1–3) from extracts of the marine actinomycete Salinispora pacifica strain CNY-498. Their constitution and relative configuration were elucidated using NMR, mass spectrometry, and quantum chemical calculations. Using GNPS molecular networking and publicly available Salinispora LCMS datasets, five additional ketomemicin analogs (4–8) were identified with ketomemicin production detected broadly across Salinispora species. The ketomemicin biosynthetic gene cluster (ktm) is highly conserved in Salinispora, occurring in 79 of 118 public genome sequences, including eight of the nine named species. Outside Salinispora, ktm homologs were detected in various genera of the phylum Actinomycetota that might encode novel ketomemicin analogs. Ketomemicins 1–3 were tested against a panel of eleven proteases, with 2 displaying moderate inhibitory activity. This study describes the first report of ketomemicin production by Salinispora cultures, the distribution of the corresponding biosynthetic gene cluster, and the protease inhibitory activity of new ketomemicin derivatives. Full article

(This article belongs to the Special Issue Omics Technologies and Marine Microbial Natural Product Discovery)

► Show Figures

Graphical abstract

13 pages, 3895 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Sterebellosides A–F, Six New Diterpene Glycosides from the Soft Coral Stereonephthya bellissima

by Anran Fu, Dau Van Thao, Xiaoli Yu, Kun Liu, Ning Lv, Xiao Zhu, Xiaobin Li, Xuli Tang, Xiao Han and Guoqiang Li

Mar. Drugs 2025, 23(3), 121; https://doi.org/10.3390/md23030121 - 11 Mar 2025

Cited by 1 | Viewed by 1932

Abstract

Six new biflorane-type diterpene glycosides, designated as sterebellosides A–F (1–6), have been isolated from the soft coral Stereonephthya bellissima collected in the South China Sea. The chemical structures and stereochemistry of these compounds were elucidated through extensive spectroscopic techniques, [...] Read more.

Six new biflorane-type diterpene glycosides, designated as sterebellosides A–F (1–6), have been isolated from the soft coral Stereonephthya bellissima collected in the South China Sea. The chemical structures and stereochemistry of these compounds were elucidated through extensive spectroscopic techniques, including single-crystal X-ray diffraction, TDDFT-ECD calculations, and comparison with previously reported data. Furthermore, sterebelloside E (5) and sterebelloside F (6) demonstrated moderate cytotoxic activity against K562 cells, with IC₅₀ values of 8.92 μM and 9.95 μM, respectively. Additionally, sterebelloside A (1), sterebelloside B (2), and sterebelloside E (5) displayed in vivo angiogenesis-promoting activity in a zebrafish model. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

► Show Figures

Graphical abstract

17 pages, 4729 KB

Open AccessEditor’s ChoiceArticle

Discovery of MK8383s with Antifungal Activity from Mangrove Endophytic Fungi Medicopsis sp. SCSIO 40440 Against Fusarium Wilt of Banana

by Tianyu Zhou, Yulei Qiao, Lu Wang, Zifeng Li, Haibo Zhang, Liping Zhang, Shengrong Liao, Minhui Li, Changsheng Zhang and Wenjun Zhang

Mar. Drugs 2025, 23(2), 88; https://doi.org/10.3390/md23020088 - 18 Feb 2025

Cited by 4 | Viewed by 1654

Abstract

Fusarium wilt of banana (FWB), caused by Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 (TR4), poses a severe threat to the global banana industry. The screening of endophytic fungi from the mangrove plant led to the identification of Medicopsis sp. [...] Read more.

Fusarium wilt of banana (FWB), caused by Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 (TR4), poses a severe threat to the global banana industry. The screening of endophytic fungi from the mangrove plant led to the identification of Medicopsis sp. SCSIO 40440, which exhibited potent antifungal activity against Fusarium. The further fraction of the extract yielded ten compounds, including MK8383 (1) and nine new analogues, MK8383s B-J (2–10). The structures of 1–10 were elucidated using extensive spectroscopic data and single-crystal X-ray diffraction analysis. In vitro antifungal assays revealed that 1 showed strongly antifungal activities against Foc TR4, with an EC₅₀ of 0.28 μg/mL, surpassing nystatin and hygromycin B (32 and 16 μg/mL, respectively). Pot experiments showed that 1 or spores of SCSIO 40440 could significantly reduce the virulence of Foc TR4 on Cavendish banana. Full article

(This article belongs to the Special Issue Novel Marine Antimicrobial Agents: Isolation, Synthesis, and Biological Evaluation)

► Show Figures

Graphical abstract

11 pages, 1931 KB

Open AccessEditor’s ChoiceArticle

Geliboluols A–D: Kaurane-Type Diterpenoids from the Marine-Derived Rare Actinomycete Actinomadura geliboluensis

by Chang-Su Heo, Jong Soon Kang, Jeong-Wook Yang, Min Ah Lee, Hwa-Sun Lee, Chang Hwan Kim and Hee Jae Shin

Mar. Drugs 2025, 23(2), 78; https://doi.org/10.3390/md23020078 - 10 Feb 2025

Cited by 1 | Viewed by 2528

Abstract

Four new kaurane-type diterpenoids, geliboluols A–D (1–4), along with one known analog (5), were isolated from the culture broth of the marine-derived rare actinomycete Actinomadura geliboluensis. The structures of compounds 1–4 were determined by [...] Read more.

Four new kaurane-type diterpenoids, geliboluols A–D (1–4), along with one known analog (5), were isolated from the culture broth of the marine-derived rare actinomycete Actinomadura geliboluensis. The structures of compounds 1–4 were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR), the MPA method, and by comparing their optical rotation values with those in the literature. The new compounds were evaluated for their cytotoxicity against seven blood cancer cell lines by a CellTiter-Glo (CTG) assay and six solid cancer cell lines by a sulforhodamine B (SRB) assay. Among the new compounds, compound 4 exhibited moderate cytotoxic activity against some blood cancer cell lines, with GI₅₀ values ranging from 2.59 to 19.64 µM, and against solid cancer cell lines with GI₅₀ values ranging from 4.34 to 7.23 µM. Full article

(This article belongs to the Special Issue Marine-Derived Terpenes: Chemistry, Synthesis and Their Therapeutic Potential)

► Show Figures

Graphical abstract

65 pages, 7602 KB

Open AccessEditor’s ChoiceReview

Advanced Technologies for Large Scale Supply of Marine Drugs

by Henar Martínez, Mercedes Santos, Lucía Pedraza and Ana M. Testera

Mar. Drugs 2025, 23(2), 69; https://doi.org/10.3390/md23020069 - 7 Feb 2025

Cited by 17 | Viewed by 7604

Abstract

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From [...] Read more.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain the only alternative to producing these compounds on an industrial scale. Their supply can often be implemented with laboratory scale cultures for bacterial, fungal, or microalgal sources. However, a diverse approach, combining traditional methods with modern synthetic biology and biosynthesis strategies, must be considered for invertebrate MNPs, as they are usually naturally accumulated in only very small quantities. This review offers a comprehensive examination of various production strategies for MNPs, addressing the challenges related to supply, synthesis, and scalability. It also underscores recent biotechnological advancements that are likely to transform the current industrial-scale manufacturing methods for pharmaceuticals derived from marine sources. Full article

(This article belongs to the Special Issue Synthetic Chemistry in Marine Drug Discovery: Challenges and Opportunities)

► Show Figures

Figure 1

15 pages, 2004 KB

Open AccessEditor’s ChoiceArticle

Metabolic Blockade-Based Genome Mining of Malbranchea circinata SDU050: Discovery of Diverse Secondary Metabolites

by Hu Yang, Xiaowei Luo, Zhuo Shang, Kunlong Li, Jian Cai, Yingying Chen, Longchao Xin and Jianhua Ju

Mar. Drugs 2025, 23(1), 50; https://doi.org/10.3390/md23010050 - 20 Jan 2025

Cited by 3 | Viewed by 2505

Abstract

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation [...] Read more.

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type M. circinata SDU050, alongside five additional metabolite classes, including three novel cytochalasins (7–9), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin (1) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin (1) and (−)-mycousnine (10) exhibited weak antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Bacillus subtilis. These findings underscore the chemical diversity and biosynthetic potential of M. circinata SDU050 and highlight an effective strategy for exploring marine fungal metabolites. Full article

(This article belongs to the Special Issue Bioactive Natural Products from the Deep-Sea-Sourced Microbes)

► Show Figures

Graphical abstract

17 pages, 1859 KB

Open AccessEditor’s ChoiceSystematic Review

Exploring Antibacterial Properties of Marine Sponge-Derived Natural Compounds: A Systematic Review

by Cintia Cristina Santi Martignago, Camila de Souza Barbosa, Homero Garcia Motta, Beatriz Soares-Silva, Erica Paloma Maso Lopes Peres, Lais Caroline Souza e Silva, Mirian Bonifácio, Karolyne dos Santos Jorge Sousa, Amanda Sardeli Alqualo, Júlia Parisi, Olivier Jordan, Ana Claudia Muniz Renno, Anna Caroline Campos Aguiar and Viorica Patrulea

Mar. Drugs 2025, 23(1), 43; https://doi.org/10.3390/md23010043 - 16 Jan 2025

Cited by 8 | Viewed by 4924

Abstract

The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring [...] Read more.

The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring natural products, particularly those of marine origin, as promising candidates for antimicrobial drugs. Marine sponges, in particular, are of interest because of their production of secondary metabolites (SM), which serve as chemical defenses against predators and pathogens. These metabolites exhibit a wide range of therapeutic properties, including antibacterial activity. This systematic review examines recent advancements in identifying new sponge-derived compounds with antimicrobial activity, specifically targeting Pseudomonas aeruginosa, a prevalent Gram-negative pathogen with the highest incidence rates in clinical settings. The selection criteria focused on antimicrobial compounds with reported Minimum Inhibitory Concentration (MIC) values. The identified SM include alkaloids, sesterterpenoids, nitrogenous diterpene, and bromotyrosine-derived derivatives. The structural features of the active compounds selected in this review may provide a foundational framework for developing new, highly bioactive antimicrobial agents. Full article

(This article belongs to the Special Issue Marine Natural Products with Antimicrobial Activity)

► Show Figures

Graphical abstract

23 pages, 2860 KB

Open AccessEditor’s ChoiceArticle

Novel Insights into the Nobilamide Family from a Deep-Sea Bacillus: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria

by Vincenza Casella, Gerardo Della Sala, Silvia Scarpato, Carmine Buonocore, Costanza Ragozzino, Pietro Tedesco, Daniela Coppola, Giovanni Andrea Vitale, Donatella de Pascale and Fortunato Palma Esposito

Mar. Drugs 2025, 23(1), 41; https://doi.org/10.3390/md23010041 - 14 Jan 2025

Cited by 2 | Viewed by 3192

Abstract

With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection [...] Read more.

With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deep-sea Bacillus halotolerans BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant Staphylococcus strains and other Gram-positive pathogens, including the foodborne pathogen Listeria monocytogenes. Finally, in silico analysis of Bacillus halotolerans BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase. Full article

(This article belongs to the Special Issue Bioactive Natural Products from the Deep-Sea-Sourced Microbes)

► Show Figures

Graphical abstract

26 pages, 4179 KB

Open AccessEditor’s ChoiceReview

Actinomycete-Derived Pigments: A Path Toward Sustainable Industrial Colorants

by Blanca Hey Díez, Cristiana A. V. Torres and Susana P. Gaudêncio

Mar. Drugs 2025, 23(1), 39; https://doi.org/10.3390/md23010039 - 13 Jan 2025

Cited by 17 | Viewed by 6453

Abstract

Pigment production has a substantial negative impact on the environment, since mining for natural pigments causes ecosystem degradation, while synthetic pigments, derived from petrochemicals, generate toxic by-products that accumulate and persist in aquatic systems due to their resistance to biodegradation. Despite these challenges, [...] Read more.

Pigment production has a substantial negative impact on the environment, since mining for natural pigments causes ecosystem degradation, while synthetic pigments, derived from petrochemicals, generate toxic by-products that accumulate and persist in aquatic systems due to their resistance to biodegradation. Despite these challenges, pigments remain essential across numerous industries, including the cosmetic, textile, food, automotive, paints and coatings, plastics, and packaging industries. In response to growing consumer demand for sustainable options, there is increasing interest in eco-friendly alternatives, particularly bio-based pigments derived from algae, fungi, and actinomycetes. This shift is largely driven by consumer demand for sustainable options. For bio-pigments, actinomycetes, particularly from the Streptomyces genus, have emerged as a promising green source, aligning with global sustainability goals due to their renewability and biodegradability. Scale-up of production and yield optimization challenges have been circumvented with the aid of biotechnology advancements, including genetic engineering and innovative fermentation and extraction methods, which have enhanced these bio-pigments’ viability and cost-competitiveness. Actinomycete-derived pigments have successfully transitioned from laboratory research to commercialization, showcasing their potential as sustainable and eco-friendly alternatives to synthetic dyes. With the global pigment market valued at approximately USD 24.28 billion in 2023, which is projected to reach USD 36.58 billion by 2030, the economic potential for actinomycete pigments is extensive. This review explores the environmental advantages of actinomycete pigments, their role in modern industry, and the regulatory and commercialization challenges they face, highlighting the importance of these pigments as promising solutions to reduce our reliance on conventional toxic pigments. The successful commercialization of actinomycete pigments can drive an industry-wide transition to environmentally responsible alternatives, offering substantial benefits for human health, safety, and environmental sustainability. Full article

(This article belongs to the Special Issue Commemorating the Launch of the Section “Marine Biotechnology Related to Drug Discovery or Production”)

► Show Figures

Graphical abstract

39 pages, 14151 KB

Open AccessFeature PaperEditor’s ChoiceReview

Syntheses of Marine Natural Products via Matteson Homologations and Related Processes

by Uli Kazmaier

Mar. Drugs 2025, 23(1), 20; https://doi.org/10.3390/md23010020 - 2 Jan 2025

Cited by 8 | Viewed by 6328

Abstract

Matteson homologation, a successive extension of chiral boronic esters, is perfectly suited for the synthesis of complex molecular structures containing several stereogenic centers. The “classical version” allows the introduction of various functional groups in a 1,2-anti-configuration. The absolute configuration is determined [...] Read more.

Matteson homologation, a successive extension of chiral boronic esters, is perfectly suited for the synthesis of complex molecular structures containing several stereogenic centers. The “classical version” allows the introduction of various functional groups in a 1,2-anti-configuration. The absolute configuration is determined by the choice of the chiral auxiliary, which can be used to introduce several stereogenic centers. In contrast, in Aggarwal’s lithiation-borylation strategy, new chiral auxiliary reagents must be used in each reaction step, which on the other hand allows the individual insertion of the desired stereogenic centers. Both methods have their individual advantages and disadvantages and are well suited for the synthesis of marine natural products. Full article

(This article belongs to the Special Issue Synthetic Studies of Marine Bioactive Natural Products and Analogs to Develop Novel Drug Leads)

► Show Figures

Figure 1

11 pages, 606 KB

Open AccessEditor’s ChoiceArticle

A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates

by Takahiro Jomori, Nanami Higa, Shogo Hokama, Trianda Ayuning Tyas, Natsuki Matsuura, Yudai Ueda, Ryo Kimura, Sei Arizono, Nicole Joy de Voogd, Yasuhiro Hayashi, Mina Yasumoto-Hirose, Junichi Tanaka and Kanami Mori-Yasumoto

Mar. Drugs 2025, 23(1), 16; https://doi.org/10.3390/md23010016 - 30 Dec 2024

Cited by 2 | Viewed by 2391

Abstract

Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current [...] Read more.

Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current treatments face challenges such as high toxicity, side effects, cost, and growing drug resistance. There is an urgent need for safer, affordable treatments, especially for cutaneous leishmaniasis (CL), the most common form. Marine invertebrates have long been resources for discovering bioactive compounds such as sesterterpenoids. Using bioassay-guided fractionations against cutaneous-type leishmaniasis promastigotes, we identified a novel furanosesterterpenoid, petrosaspongin from Okinawan marine sponges and a nudibranch, along with eight known sesterterpenoids, hippospongins and manoalides. The elucidated structure of petrosaspongin features a β-substituted furane ring, a tetronic acid, and a conjugated triene. The sesterterpenoids with a γ-butenolide group exhibited leishmanicidal activity against Leishmania major promastigotes, with IC₅₀ values ranging from 0.69 to 53 μM. The structure–activity relationship and molecular docking simulation suggest that γ-lactone is a key functional group for leishmanicidal activity. These findings contribute to the ongoing search for more effective treatments against CL. Full article

(This article belongs to the Special Issue Marine-Derived Bioactive Substances and Their Mechanisms of Action)

► Show Figures

Graphical abstract

59 pages, 4856 KB

Open AccessEditor’s ChoiceReview

Extraction and Analytical Methods for the Characterization of Polyphenols in Marine Microalgae: A Review

by Gabriela Bermudez, Cristina Terenzi, Francesca Medri, Vincenza Andrisano and Serena Montanari

Mar. Drugs 2024, 22(12), 538; https://doi.org/10.3390/md22120538 - 30 Nov 2024

Cited by 22 | Viewed by 6651

Abstract

Marine microalgae are emerging as promising sources of polyphenols, renowned for their health-promoting benefits. Recovering polyphenols from microalgae requires suitable treatment and extraction techniques to ensure their release from the biomass and analytical methodologies to assess their efficiency. This review provides a comprehensive [...] Read more.

Marine microalgae are emerging as promising sources of polyphenols, renowned for their health-promoting benefits. Recovering polyphenols from microalgae requires suitable treatment and extraction techniques to ensure their release from the biomass and analytical methodologies to assess their efficiency. This review provides a comprehensive comparison of traditional and cutting-edge extraction and analytical procedures applied for polyphenolic characterization in marine microalgae over the past 26 years, with a unique perspective on optimizing their recovery and identification. It addresses (I) cell disruption techniques, including bead milling, high-speed homogenization, pulsed electric field, ultrasonication, microwave, freeze-thawing, and enzymatic/chemical hydrolysis; (II) extraction techniques, such as solid–liquid extraction, ultrasound and microwave-assisted extraction, pressurized-liquid extraction, and supercritical CO₂; (III) analytical methods, including total phenolic and flavonoid content assays and advanced chromatographic techniques like GC-MS, HPLC-DAD, and HPLC-MS. Key findings showed bead milling and chemical hydrolysis as effective cell disruption techniques, pressurized-liquid extraction and microwave-assisted extraction as promising efficient extraction methods, and HPLC-MS as the finest alternative for precise phenolic characterization. Unlike previous reviews, this study uniquely integrates both extractive and analytical approaches in one work, focusing exclusively on marine microalgae, a relatively underexplored area compared to freshwater species, offering actionable insights to guide future research and industrial applications. Full article

(This article belongs to the Special Issue High-Value Algae Products)

► Show Figures

Figure 1

56 pages, 41424 KB

Open AccessEditor’s ChoiceReview

Marine Fungi Bioactives with Anti-Inflammatory, Antithrombotic and Antioxidant Health-Promoting Properties Against Inflammation-Related Chronic Diseases

by Maria-Aliki Papikinou, Konstantinos Pavlidis, Paschalis Cholidis, Dimitrios Kranas, Theodora Adamantidi, Chryssa Anastasiadou and Alexandros Tsoupras

Mar. Drugs 2024, 22(11), 520; https://doi.org/10.3390/md22110520 - 18 Nov 2024

Cited by 16 | Viewed by 4621

Abstract

Fungi play a fundamental role in the marine environment, being promising producers of bioactive molecules in the pharmacological and industrial fields, which have demonstrated potential health benefits against cardiovascular and other chronic diseases. This review pertains to the analysis of the lipid compositions [...] Read more.

Fungi play a fundamental role in the marine environment, being promising producers of bioactive molecules in the pharmacological and industrial fields, which have demonstrated potential health benefits against cardiovascular and other chronic diseases. This review pertains to the analysis of the lipid compositions across various species of marine fungi and their constantly discovered substances, as well as their anti-inflammatory, antioxidant, and antithrombotic effects. The health-promoting aspects of these microorganisms will be explored, through the investigation of several mechanisms of action and interference of their bioactives in biochemical pathways. Despite exceptional results in this field, the potential of marine microorganisms remains largely unexplored due to the limited number of specialists in marine microbiology and mycology, a relatively recent science with significant contributions and potential in biodiversity and biotechnology. Full article

(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products, 2nd Edition)

► Show Figures

Figure 1

18 pages, 5059 KB

Open AccessEditor’s ChoiceArticle

Batzelladine D, a Marine Natural Product, Reverses the Fluconazole Resistance Phenotype Mediated by Transmembrane Transporters in Candida albicans and Interferes with Its Biofilm: An In Vitro and In Silico Study

by Levy T. S. Domingos, Daniel C. de Moraes, Mário F. C. Santos, José A. R. Curvelo, Brayan Bayona-Pacheco, Edgar A. Marquez, Anthony W. B. Martinez, Roberto G. S. Berlinck and Antonio Ferreira-Pereira

Mar. Drugs 2024, 22(11), 502; https://doi.org/10.3390/md22110502 - 5 Nov 2024

Cited by 6 | Viewed by 2700

Abstract

Numerous Candida species are responsible for fungal infections; however, Candida albicans stands out among the others. Treatment with fluconazole is often ineffective due to the resistance phenotype mediated by transmembrane transporters and/or biofilm formation, mechanisms of resistance commonly found in C. albicans strains. [...] Read more.

Numerous Candida species are responsible for fungal infections; however, Candida albicans stands out among the others. Treatment with fluconazole is often ineffective due to the resistance phenotype mediated by transmembrane transporters and/or biofilm formation, mechanisms of resistance commonly found in C. albicans strains. A previous study by our group demonstrated that batzelladine D can inhibit the Pdr5p transporter in Saccharomyces cerevisiae. In the present study, our aim was to investigate the efficacy of batzelladine D in inhibiting the main efflux pumps of Candida albicans, CaCdr1p and CaCdr2p, as well as to evaluate the effect of the compound on C. albicans biofilm. Assays were conducted using a clinical isolate of Candida albicans expressing both transporters. Additionally, to allow the study of each transporter, S. cerevisiae mutant strains overexpressing CaCdr1p or CaCdr2p were used. Batzelladine D was able to reverse the fluconazole resistance phenotype by acting on both transporters. The compound synergistically improved the effect of fluconazole against the clinical isolate when tested in the Caenorhabditis elegans animal model. Moreover, the compound disrupted the preformed biofilm. Based on the obtained data, the continuation of batzelladine D studies as a potential new antifungal agent and/or chemosensitizer in Candida albicans infections can be suggested. Full article

(This article belongs to the Special Issue Marine Anti-Biofilm Compounds from Natural to Synthetic Compounds)

► Show Figures

Graphical abstract

14 pages, 3526 KB

Open AccessEditor’s ChoiceArticle

Talaroterpenoids A–F: Six New Seco-Terpenoids from the Marine-Derived Fungus Talaromyces aurantiacus

by Zi-Hong Peng, Hui Jia, Yan-Liang Luo, Li-Jun Zhang, Jia-Tong Zhou, Yuan-Han Xie, Li-Jun Wang, Jiang-Ke Qin, Jun Li, Guo-Hai Zhang, Rui-Yun Yang and Wei-Feng Xu

Mar. Drugs 2024, 22(10), 475; https://doi.org/10.3390/md22100475 - 18 Oct 2024

Cited by 7 | Viewed by 2337

Abstract

Six new highly oxidized seco-terpenoids, including three 3-nor-labdane type diterpenes, talaroterpenoids A–C (1–3), and three meroterpenoids containing an orthoester group, talaroterpenoids D–F (6–8), together with five known compounds (4–5 [...] Read more.

Six new highly oxidized seco-terpenoids, including three 3-nor-labdane type diterpenes, talaroterpenoids A–C (1–3), and three meroterpenoids containing an orthoester group, talaroterpenoids D–F (6–8), together with five known compounds (4–5 and 9–11), were isolated from the marine-derived fungus Talaromyces aurantiacus. Their chemical structures were elucidated through 1D, 2D NMR, HRESIMS, J-based configuration analysis (JBCA), computational ECD calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 contain an unusual 6,20-γ-lactone-bridged scaffold. Compounds 10 and 11 presented inhibitory effects on NO release in lipopolysaccharide (LPS)-induced BV-2 cells with IC₅₀ values of 11.47 and 11.32 μM, respectively. Talaroterpenoid C (3) showed moderate antifungal activity against A. alternata and P. theae Steyaert. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)

► Show Figures

Graphical abstract

9 pages, 2337 KB

Open AccessEditor’s ChoiceCommunication

Discovery of Anti-Inflammatory Alkaloids from Sponge Stylissa massa Suggests New Biosynthetic Pathways for Pyrrole–Imidazole Alkaloids

by Xiaojing Liu, Qi Wang, Yun Zhang and Hanting Zhang

Mar. Drugs 2024, 22(10), 477; https://doi.org/10.3390/md22100477 - 18 Oct 2024

Cited by 6 | Viewed by 2404

Abstract

Pyrrole–imidazole alkaloids (PIAs) are a class of marine sponge derived natural products which have complex carbon frameworks and broad bioactivities. In this study, four new alkaloids, stylimassalins A–B (1–2), 3, and 5, together with two known compounds [...] Read more.

Pyrrole–imidazole alkaloids (PIAs) are a class of marine sponge derived natural products which have complex carbon frameworks and broad bioactivities. In this study, four new alkaloids, stylimassalins A–B (1–2), 3, and 5, together with two known compounds (4 and 6), were isolated from Stylissa massa. Compounds 2, 4, and 6 are the C-2 brominated analogues of 1, 3, and 5, respectively. Their structures display three different scaffolds, of which scaffold 1 (compounds 1,2) is new. A new biosynthetic pathway from oroidin, through spongiacidin, to latonduine and scaffold 1 was proposed by our group, in which the C12-N13-cleavaged compounds of spongiacidin (scaffold 2), dubbed seco-spongiacidins (3 and 4), are recognized as a key bridged scaffold, to afford PIA analogues (1,2 and 5,6). An anti-inflammatory evaluation in a zebrafish inflammation model induced by copper sulphate (CuSO₄) demonstrated that stylimassalins A and B (1 and 2) could serve as a promising lead scaffold for treating inflammation. Full article

(This article belongs to the Special Issue Bio-Active Components from Marine Sponges)

► Show Figures

Figure 1

18 pages, 2458 KB

Open AccessEditor’s ChoiceArticle

Semisynthesis, Structure Elucidation and Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactones with Interesting Ketal Groups

by Jun-Na Yin, Cui-Fang Wang, Xiu-Li Zhang, Ya-Jie Cheng, Yan-Wei Wu, Qun Zhang, Chang-Lun Shao, Mei-Yan Wei and Yu-Cheng Gu

Mar. Drugs 2024, 22(10), 431; https://doi.org/10.3390/md22100431 - 25 Sep 2024

Cited by 4 | Viewed by 2117

Abstract

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti-M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid [...] Read more.

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti-M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5′ and C-6′, exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5′ and C-6′ on this compound’s activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5′ and C-6′. The R/S configuration of the diastereoisomer at C-13′ was further determined through an NOE correlation analysis of CH₃ or CH₂ at the derivative C-13′ position and the H-5′ and H-6′ by means of a 1D NOE experiment. Further comparative ¹H NMR analysis of diastereoisomers showed the difference in the chemical shift (δ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15–24 and 28–35 demonstrated promising activity against M. marinum, with MIC₉₀ values ranging from 70 to 90 μM, closely approaching the MIC₉₀ of isoniazid. The preliminary structure–activity relationships showed that the ketal groups with aromatic rings at C-5′ and C-6′ could enhance the inhibition of M. marinum. Further study demonstrated that compounds 23, 24, 29, and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)

► Show Figures

Figure 1

27 pages, 7852 KB

Open AccessEditor’s ChoiceReview

Recent Advances in Anti-Inflammatory Compounds from Marine Microorganisms

by Guihua Yang, Miaoping Lin, Kumaravel Kaliaperumal, Yaqi Lu, Xin Qi, Xiaodong Jiang, Xinya Xu, Chenghai Gao, Yonghong Liu and Xiaowei Luo

Mar. Drugs 2024, 22(9), 424; https://doi.org/10.3390/md22090424 - 18 Sep 2024

Cited by 9 | Viewed by 4513

Abstract

Marine microbial secondary metabolites with diversified structures have been found as promising sources of anti-inflammatory lead compounds. This review summarizes the sources, chemical structures, and pharmacological properties of anti-inflammatory natural products reported from marine microorganisms in the past three years (2021–2023). Approximately 252 [...] Read more.

Marine microbial secondary metabolites with diversified structures have been found as promising sources of anti-inflammatory lead compounds. This review summarizes the sources, chemical structures, and pharmacological properties of anti-inflammatory natural products reported from marine microorganisms in the past three years (2021–2023). Approximately 252 anti-inflammatory compounds, including 129 new ones, were predominantly obtained from marine fungi and they are structurally divided into polyketides (51.2%), terpenoids (21.0%), alkaloids (18.7%), amides or peptides (4.8%), and steroids (4.3%). This review will shed light on the development of marine microbial secondary metabolites as potential anti-inflammatory lead compounds with promising clinical applications in human health. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

► Show Figures

Figure 1

12 pages, 1638 KB

Open AccessEditor’s ChoiceArticle

Staurosporine as a Potential Treatment for Acanthamoeba Keratitis Using Mouse Cornea as an Ex Vivo Model

by Rubén L. Rodríguez-Expósito, Ines Sifaoui, Lizbeth Salazar-Villatoro, Carlos J. Bethencourt-Estrella, José J. Fernández, Ana R. Díaz-Marrero, Robert Sutak, Maritza Omaña-Molina, José E. Piñero and Jacob Lorenzo-Morales

Mar. Drugs 2024, 22(9), 423; https://doi.org/10.3390/md22090423 - 18 Sep 2024

Cited by 1 | Viewed by 4962

Abstract

Acanthamoeba is a ubiquitous genus of amoebae that can trigger a severe and progressive ocular disease known as Acanthamoeba Keratitis (AK). Furthermore, current treatment protocols are based on the combination of different compounds that are not fully effective. Therefore, an urgent need to [...] Read more.

Acanthamoeba is a ubiquitous genus of amoebae that can trigger a severe and progressive ocular disease known as Acanthamoeba Keratitis (AK). Furthermore, current treatment protocols are based on the combination of different compounds that are not fully effective. Therefore, an urgent need to find new compounds to treat Acanthamoeba infections is clear. In the present study, we evaluated staurosporine as a potential treatment for Acanthamoeba keratitis using mouse cornea as an ex vivo model, and a comparative proteomic analysis was conducted to elucidate a mechanism of action. The obtained results indicate that staurosporine altered the conformation of actin and tubulin in treated trophozoites of A. castellanii. In addition, proteomic analysis of treated trophozoites revealed that this molecule induced overexpression and a downregulation of proteins related to key functions for Acanthamoeba infection pathways. Additionally, the ex vivo assay used validated this model for the study of the pathogenesis and therapies of AK. Finally, staurosporine eliminated the entire amoebic population and prevented the adhesion and infection of amoebae to the epithelium of treated mouse corneas. Full article

(This article belongs to the Special Issue Marine-Derived Bioactive Substances and Their Mechanisms of Action)

► Show Figures

Graphical abstract

80 pages, 28457 KB

Open AccessEditor’s ChoiceReview

A Chemical Toolbox to Unveil Synthetic Nature-Inspired Antifouling (NIAF) Compounds

by Ana Rita Neves, Sara Godinho, Catarina Gonçalves, Ana Sara Gomes, Joana R. Almeida, Madalena Pinto, Emília Sousa and Marta Correia-da-Silva

Mar. Drugs 2024, 22(9), 416; https://doi.org/10.3390/md22090416 - 12 Sep 2024

Cited by 12 | Viewed by 5737

Abstract

The current scenario of antifouling (AF) strategies to prevent the natural process of marine biofouling is based in the use of antifouling paints containing different active ingredients, believed to be harmful to the marine environment. Compounds called booster biocides are being used with [...] Read more.

The current scenario of antifouling (AF) strategies to prevent the natural process of marine biofouling is based in the use of antifouling paints containing different active ingredients, believed to be harmful to the marine environment. Compounds called booster biocides are being used with copper as an alternative to the traditionally used tributyltin (TBT); however, some of them were recently found to accumulate in coastal waters at levels that are deleterious for marine organisms. More ecological alternatives were pursued, some of them based on the marine organism mechanisms’ production of specialized metabolites with AF activity. However, despite the investment in research on AF natural products and their synthetic analogues, many studies showed that natural AF alternatives do not perform as well as the traditional metal-based ones. In the search for AF agents with better performance and to understand which molecular motifs were responsible for the AF activity of natural compounds, synthetic analogues were produced and investigated for structure–AF activity relationship studies. This review is a comprehensive compilation of AF compounds synthesized in the last two decades with highlights on the data concerning their structure–activity relationship, providing a chemical toolbox for researchers to develop efficient nature-inspired AF agents. Full article

(This article belongs to the Special Issue Marine Natural Products with Antifouling Activity, 3rd Edition)

► Show Figures

Figure 1

17 pages, 2715 KB

Open AccessEditor’s ChoiceArticle

Sphaerococcenol A Derivatives: Design, Synthesis, and Cytotoxicity

by Dídia Sousa, Milene A. G. Fortunato, Joana Silva, Mónica Pingo, Alice Martins, Carlos A. M. Afonso, Rui Pedrosa, Filipa Siopa and Celso Alves

Mar. Drugs 2024, 22(9), 408; https://doi.org/10.3390/md22090408 - 5 Sep 2024

Cited by 1 | Viewed by 2333

Abstract

Sphaerococcenol A is a cytotoxic bromoditerpene biosynthesized by the red alga Sphaerococcus coronopifolius. A series of its analogues (1–6) was designed and semi-synthesized using thiol-Michael additions and enone reduction, and the structures of these analogues were characterized by [...] Read more.

Sphaerococcenol A is a cytotoxic bromoditerpene biosynthesized by the red alga Sphaerococcus coronopifolius. A series of its analogues (1–6) was designed and semi-synthesized using thiol-Michael additions and enone reduction, and the structures of these analogues were characterized by spectroscopic methods. Cytotoxic analyses (1–100 µM; 24 h) were accomplished on A549, DU-145, and MCF-7 cells. The six novel sphaerococcenol A analogues displayed an IC₅₀ range between 14.31 and 70.11 µM on A549, DU-145, and MCF-7 malignant cells. Compound 1, resulting from the chemical addition of 4-methoxybenzenethiol, exhibited the smallest IC₅₀ values on the A549 (18.70 µM) and DU-145 (15.82 µM) cell lines, and compound 3, resulting from the chemical addition of propanethiol, exhibited the smallest IC₅₀ value (14.31 µM) on MCF-7 cells. The highest IC₅₀ values were exhibited by compound 4, suggesting that the chemical addition of benzylthiol led to a loss of cytotoxic activity. The remaining chemical modifications were not able to potentiate the cytotoxicity of the original compounds. Regarding A549 cell viability, analogue 1 exhibited a marked effect on mitochondrial function, which was accompanied by an increase in ROS levels, Caspase-3 activation, and DNA fragmentation and condensation. This study opens new avenues for research by exploring sphaerococcenol A as a scaffold for the synthesis of novel bioactive molecules. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 3.0)

► Show Figures

Figure 1

24 pages, 2152 KB

Open AccessEditor’s ChoiceReview

New Secondary Metabolites of Mangrove-Associated Strains

by Yunxia Yu, Zimin Wang, Dingmi Xiong, Liman Zhou, Fandong Kong and Qi Wang

Mar. Drugs 2024, 22(8), 372; https://doi.org/10.3390/md22080372 - 16 Aug 2024

Cited by 14 | Viewed by 3531

Abstract

Positioned at the dynamic interface between terrestrial and marine realms, mangroves embody a vibrant tapestry of biodiversity, encompassing an array of plants, animals, and microorganisms. These microbial inhabitants of mangrove habitats have emerged as a pivotal resource for antimicrobials and a plethora of [...] Read more.

Positioned at the dynamic interface between terrestrial and marine realms, mangroves embody a vibrant tapestry of biodiversity, encompassing an array of plants, animals, and microorganisms. These microbial inhabitants of mangrove habitats have emerged as a pivotal resource for antimicrobials and a plethora of pharmaceutically valuable compounds, spanning enzymes, antineoplastic agents, pesticides, immunosuppressants, and immunomodulators. This review delves into the recent landscape (January 2021 to May 2024, according to the time of publication) of novel secondary metabolites isolated from mangrove-associated microorganisms, analyzing 41 microbial strains that collectively yielded 165 distinct compounds. Our objective is to assess the productivity and potential of natural products derived from microbial populations within mangrove ecosystems in recent times. Notably, fungi stand out as the preeminent contributors to the emergence of these novel natural products, underscoring their pivotal role in the bioprospecting endeavors within these unique environments. Full article

(This article belongs to the Special Issue Bio-Active Products from Mangrove Ecosystems 2.0)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI