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Review

Marine Fungal Metabolites as Potential Antidiabetic Agents: A Comprehensive Review of Their Structures and Enzyme Inhibitory Activities

by
Zimin Wang
1,3,†,
Meirong Zhao
2,†,
Yunxia Yu
3,
Fandong Kong
3,*,
Nanxin Lin
3,* and
Qi Wang
1,*
1
Department of Pediatric intensive Care Medicine, Hainan Women and Children’s Medical Center, Haikou 570100, China
2
College of Food and Pharmaceutical Engineering, Guangxi Vocational University of Agriculture, Nanning 530006, China
3
Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Polysaccharide Materials and Modification, School of of Marine Science and Biotechnology, Guangxi Minzu University, Nanning 530006, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Mar. Drugs 2025, 23(4), 142; https://doi.org/10.3390/md23040142
Submission received: 24 February 2025 / Revised: 18 March 2025 / Accepted: 24 March 2025 / Published: 26 March 2025
(This article belongs to the Special Issue Bioactive Secondary Metabolites of Marine Fungi, 3rd Edition)
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Abstract

:
Diabetes mellitus has emerged as a global public health crisis, with Type 2 diabetes (T2D) constituting over 90% of cases. Current treatments are palliative, primarily focusing on blood glucose modulation. This review systematically evaluates 181 bioactive compounds isolated from 66 marine fungal strains for their inhibitory activities against key diabetes-related enzymes, including α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), dipeptidyl peptidase-4 (DPP-4), glycogen synthase kinase-3β (GSK-3β), and fatty acid-binding protein 4 (FABP4). These compounds, categorized into polyketides, alkaloids, terpenoids, and lignans, exhibit multitarget engagement and nanomolar-to-micromolar potency. The review highlights the potential of marine fungal metabolites as novel antidiabetic agents, emphasizing their structural novelty and diverse mechanisms of action. Future research should focus on overcoming challenges related to yield and extraction, leveraging advanced technologies such as genetic engineering and synthetic biology to enhance drug development.

1. Introduction

Diabetes mellitus, a chronic metabolic disorder characterized by persistent hyperglycemia, has emerged as a global public health crisis. The escalating prevalence of diabetes—driven by widespread adoption of high-caloric diets, sedentary behaviors, and demographic aging—not only predisposes individuals to life-threatening complications (e.g., cardiovascular diseases, nephropathy, and retinopathy) but also imposes substantial socioeconomic burdens on healthcare systems worldwide [1]. According to the ninth edition of the International Diabetes Federation (IDF) Diabetes Atlas (2019), diabetes now ranks as the most prevalent non-communicable disease (NCD), affecting approximately 463 million adults globally [2]. Pathophysiologically, this disorder stems from metabolic dysregulation caused by absolute or relative insulin deficiency coupled with aberrant glucagon activity [3]. Despite advances in glycemic management strategies, current therapies remain palliative rather than curative, focusing primarily on delaying complications through blood glucose modulation. Clinically, diabetes is classified into insulin-dependent Type 1 diabetes (T1D) and non-insulin-dependent Type 2 diabetes (T2D), with T2D constituting >90% of total cases [4].
First-line pharmacological interventions for T2D include insulin secretagogues (e.g., sulfonylureas), biguanides (e.g., metformin), α-glucosidase inhibitors (e.g., acarbose), and insulin sensitizers (e.g., thiazolidinediones) [5]. While these agents demonstrate initial therapeutic efficacy, their long-term utility is hampered by progressive β-cell dysfunction, acquired drug resistance, and adverse effects ranging from hypoglycemia to cardiovascular risks [6]. Consequently, the development of novel antidiabetic agents with improved safety profiles and mechanisms circumventing these limitations represents a critical unmet need in diabetes research. The pathogenesis of T2D involves intricate interactions between genetic predisposition and environmental triggers, manifesting as the dysregulation of key metabolic enzymes and signaling pathways. Central to this complexity are five pivotal targets: (1) α-glucosidase, which modulates postprandial hyperglycemia via carbohydrate digestion; (2) protein tyrosine phosphatase 1B (PTP1B), an insulin receptor signaling antagonist; (3) dipeptidyl peptidase-4 (DPP-4), responsible for incretin hormone degradation; (4) glycogen synthase kinase-3β (GSK-3β), a negative regulator of glycogen synthesis; and (5) fatty acid-binding protein 4 (FABP4), a mediator of lipid-induced insulin resistance and inflammation [7]. Targeting these enzymes offers dual advantages, elucidating molecular drivers of diabetes while enabling the rational design of multitarget therapeutics.
Natural products remain indispensable in drug discovery, with >60% of FDA-approved small-molecule drugs originating from natural scaffolds [8]. Among biological sources, fungi—particularly marine-derived strains—represent an underexplored reservoir of bioactive metabolites. Marine fungi, evolutionarily adapted to extreme environments (e.g., high salinity, low temperature, and oligotrophic conditions), exhibit unique biosynthetic pathways yielding structurally novel compounds with pronounced pharmacological potential [9]. Notably, marine fungal metabolites spanning polyketides, alkaloids, and terpenoids have demonstrated inhibitory effects against diabetes-related targets, positioning them as promising candidates for antidiabetic drug development [10].
This review systematically evaluates 181 bioactive compounds isolated from 66 marine fungal strains, focusing on their inhibitory activities against α-glucosidase (IC50: 0.8–58.3 μM), PTP1B (IC50: 1.2–32.7 μM), DPP-4 (IC50: 3.4–89.1 μM), GSK-3β (IC50: 0.5–47.6 μM), and FABP4 (IC50: 2.1–75.4 μM). Representative molecules include xylarianaphthol-1 (dual α-glucosidase/PTP1B inhibition, IC50 = 2.3/4.7 μM) and aspergoterpenin C (potent GSK-3β inhibitor, IC50 = 0.5 μM) [11]. Their structural novelty, multitarget engagement, and nanomolar-to-micromolar potency underscore their potential as lead compounds for next-generation antidiabetic therapeutics.

2. Compounds

In the following sections, we will discuss these compounds based on their different structures and the activity of these compounds on diabetes-related enzymes. We divided these 181 compounds into four categories: polyketones, alkaloids, terpenes, and lignans, and their proportions are shown in Figure 1 below. These compounds were isolated from 66 strains of fungi sourced from diverse marine environments. The majority of these fungi belonged to the genera Penicillium and Aspergillus, while other fungi constituted merely 26.23%, representing a relatively small proportion. The detailed statistics are presented in Figure 1 below.

2.1. Polyketides

Polyketides, a class of natural products isolated from marine fungi, feature an extensive array of diverse structures synthesized via distinct biosynthetic pathways [12]. In the realm of diabetes drug research and development, these compounds have emerged as highly promising candidates. Their unique chemical architectures endow them with specific biological activities, positioning polyketides as strong contenders to serve as novel lead compounds for diabetes treatment. This holds the promise of introducing innovative therapeutic solutions to address the challenges posed by diabetes.
Five known compounds, emodin (1), geodin hydrate (2), methyl dichloroasterrate (3), monomethylosoic acid (4), and epicoccolide B (5), were isolated from the marine-derived Aspergillus flavipes HN4-13 collected from a Lianyungang coastal sediment sample. Compounds 1 and 4 showed noncompetitive α-glucosidase inhibition, with Ki/IC50 values of 0.79/19 μM and 2.8/90 μM, respectively. Compounds 2, 3, and 5 exhibited mixed α-glucosidase inhibition, with Ki/IC50 values of (6.3, 5.5)/55 μM, (1.4, 0.60)/9.9 μM, and (2.5, 7.2)/33 μM, respectively, compared to acarbose (IC50 101 μM) and 1-deoxynojirimycin (IC50 79 μM) [13]. Two new dibenzo-α-pyrone derivatives, alternolides B and C (6–7), and the known altenuisol alternariol 1′-hydroxy-9-methyl ether (8), were isolated from the marine-derived Alternaria alternata LW37 via the OSMAC strategy. Compounds 6, 7, and 8 inhibited α-glucosidase, with IC50 values of 725.85 ± 4.75 μM, 451.25 ± 6.95 μM, and 6.27 ± 0.68 μM, respectively. Molecular docking analysis indicated that compounds 6–8 formed three, four, and six hydrogen bonds, respectively, with α-glycosidase, which closely correlated with their experimentally determined bioactivity potencies [14].
The fungal strain Penicillium thomii YPGA3, isolated from Yap Trench sediments, yielded three new chromone derivatives, penithochromones R−T (9–11), along with two known compounds—penithochromone C (12) and penithochromone A (13). Compounds 9–13 significantly inhibited α-glucosidase, with IC50 values ranging from 268 to 1017 µM, outperforming the positive control acarbose (1.3 mmol) [15]. A new phenolic compound, epicocconigrone C (14), along with five known phenolic compounds, epicocconigrone A (15), 2-(10-formyl-11,13-dihydroxy-12-methoxy-14-methyl)-6,7-dihydroxy-5-methyl-4-benzofurancarboxaldehyde (16), epicoccolide B (17), eleganketal A (18), and 2,3,4-trihydroxy-6(hydroxymethyl)-5-methylbenzyl-alcohol (19), were isolated from Aspergillus insulicola from deep-sea sediment. Compounds 14–19 potently inhibited α-glucosidase, with IC50 values ranging from 17.04 to 292.47 µM, better than acarbose (IC50 822.97 µM). The number of hydroxyl groups in polyhydroxyphenolic compounds is crucial for α-glucosidase inhibitory activity, as reflected in the low IC50 values of compounds 15 and 17, while structures with fewer hydroxyl groups (compounds 14 and 16) exhibit minimal activity [16].
Four new polyketides—5-((R,1Z,3E)-6-hydroxy-1,3-heptadien-1-yl)-1,3-benzenediol (20), 4-carboxy-5-((R,1Z,3E)-6-hydroxy-1,3-heptadien-1-yl)-1,3-benzenediol (21), 4-carboxy-5-((1Z,3E)-1,3-heptadien-1-yl)-1,3-benzenediol (22), 5-((1Z,3E)-4-carboxy-1,3-butadienyl-1-yl)-1,3-benzenediol (23)—and three known compounds—penialidin A (24), 3,4-dihydroxybenzeneacetic acid (25), and ɛ-caprolactone derivative (26)—were isolated from Penicillium sp. TW58-16. Compounds 20–26 had strong α-glucosidase inhibitory effects, with inhibition rates of 73.2%, 55.6%, 74.4%, 32.0%, 36.9%, 88.0%, and 91.1% at 400 μM, respectively, which were comparable to or higher than that of acarbose [17].
One new p-terphenyl derivative, asperterphenylcins B (27), along with the previously described terphenyllin (28) and 3″-hydroxyterphenyllin (29), was obtained from the solid-rice culture of marine-derived Aspergillus candidus HM5-4 isolated from South China Sea sponges. Compounds 27–29 potently inhibited α-glucosidase, with IC50 values of 1.26 ± 0.19 μM, 2.16 ± 0.44 μM, and 13.22 ± 0.55 μM, respectively [18]. Three new thioester-containing benzoate derivatives, Eurothiocin C (30), Eurothiocin F (31), and Eurothiocin G (32), were isolated from the deep-sea fungus Talaromyces indigoticus FS688. Compound 30 showed potent α-glucosidase inhibitory activity, with an IC50 value of 5.4 μM, while compounds 31 and 32 had moderate inhibitory effects, with IC50 values of 33.6 μM and 72.1 μM, respectively [19]. Two pairs of novel salicylaldehyde derivative enantiomers, euroticins G (33–34) and euroticins H (35–36), along with the known compound eurotirumin (37), were isolated and characterized from the marine-derived fungus Eurotium sp. SCSIO F452. Compounds 33 to 37 inhibited α-glucosidase, with IC50 values ranging from 16.31 to 79.71 μM [20]. From the marine-derived fungus Meira sp. 1210CH-42, a new catecholic compound, meirols A (38), and a known analog, argovin (39), were isolated. Both 38 and 39 inhibited α-glucosidase, with IC50 values of 199.70 μM and 184.50 μM, respectively (acarbose, IC50 = 301.93 μM) [21]. A new depsidone, botryorhodine H (40), together with two known analogs, botryorhodine C (41) and botryorhodines D (42), was obtained from the mangrove endophytic fungus Trichoderma sp. 307 through co-culturing with Acinetobacter johnsonii B2. Compounds 40 to 42 inhibited α-glucosidase, with IC50 values ranging from 8.1 to 11.2 μM [22]. A new chromone, 7-hydroxy-5-methoxy-2,3-dimethylchromone (43), and two known metabolites, 2,3-dihydro-5-methoxy-2-methylchromen-4-one (44) and helicascolides A (45), were isolated from the mangrove-derived fungus Daldinia eschscholtzii HJ004. Compounds 43 to 45 inhibited α-glucosidase, with IC50 values of 13 μM, 15 μM, and 16 μM, respectively [23]. Epicoccolide B (46), a known compound, was isolated from the mangrove fungus Mycosphaerella sp. SYSU-DZG01 and inhibited α-glucosidase, with an IC50 value of 26.7 μM [24]. Chemical investigation of the endophytic fungus Aspergillus sp. 16-5B, cultured on Czapek’s medium, led to the isolation of two new metabolites, aspergifuranone (47) and isocoumarin derivative 3,4-Dihydro-4,6,8-trihydroxy-3-methoxy-3,7-dimethyl-1H-2-benzopyran-1-one (48), along with the known pestaphthalide A (49). Compound 47 showed significant α-glucosidase inhibitory activity, with an IC50 value of 9.05 ± 0.60 μM. Compounds 48 and 49 had moderate inhibitory activities, with IC50 values of 90.4 μM and 96.6 μM, respectively [25].
Three biosynthetically related known analogs, penicidone C (50), penicillide (51), and Sch725680 (52), were obtained from the culture of a mangrove sediment-derived fungus Penicillium pinophilum SCAU037. Compounds 50 to 52 significantly inhibited α-glucosidase, with IC50 values of 51.9, 78.4, and 33.8 µM, respectively [26]. Two new compounds, 53 and 54, which have not yet been named, along with two known compounds, peniciaculin A (55) and expansol D (56), were isolated from the culture of the endophytic fungus Aspergillus flavus QQSG-3 sourced from a fresh branch of Kandelia obobata collected in Huizhou, Guangdong, China. Compounds 53 to 56 strongly inhibited α-glucosidase, with IC50 values ranging from 1.5 to 4.5 µM [27]. The extraction and isolation of marine sediment Penicillium species collected in Vietnam yielded a known compound, 2′,3′-dihydrosorbicillin (57), which potentially inhibited α-glucosidase at a concentration of 2.0 mM, with an inhibition rate of 66.31% [28]. A new flavone, aspergivone B (58), was isolated from the fungus Aspergillus candidus cultured from the gorgonian coral Anthogorgia ochracea collected in the South China Sea. It slightly inhibited α-glucosidase, with an IC50 value of 244 µg/mL [29]. A new naphthoquinone, 5-hydroxy-2-methoxynaphtho[9–c]furan-1,4-dione (59), and a known compound, 2-acetyl-7-methoxybenzofuran (60), were obtained from the EtOAc extract of the mangrove-derived fungus Daldinia eschscholtzii HJ004. They potently inhibited α-glucosidase, with IC50 values of 5.7 and 1.1 µg/mL, respectively [30]. A chemical investigation of P. brefeldianum F4a, using an activity-guided isolation approach, led to the discovery of a novel compound, peniorcinol C (61). This compound significantly inhibited α-glucosidase, with an IC50 value of 38.98 µg/mL [31]. Two new de-O-methyllasiodiplodins, (3R,7R)-7-hydroxy-de-O-methyllasiodiplodin (62) and (3R)-5-oxo-de-O-methyllasiodiplodin (63), were isolated from the co-cultivation of the mangrove endophytic fungus Trichoderma sp. 307 and the aquatic pathogenic bacterium Acinetobacter johnsonii B2. Both 62 and 63 potently inhibited α-glucosidase, with IC50 values of 25.8 and 54.6 µM, respectively, surpassing the positive control acarbose (IC50 = 703.8 µM) [32]. Four new compounds, including two chlorinated diphenyl ethers, chrysine B (64) and chrysine C (65), one dichlorinated xanthone, chrysoxanthone (66), and a new compound dichloroorcinol (67), along with five known compounds, methyl 3′methoxy-3,5-dichloroasterric acid (68), 2,4-dichloroasterric acid (69), methyl chloroasterrate(70), mono-chlorosulochrin (71), and (+)-geodin (72), were isolated from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001. Compounds 64–72 inhibited α-glucosidase, with IC50 values ranging from 0.04 to 0.35 mM (IC50 0.28 mM for acarbose) [33]. A new phenylpropanoid derivative (73) was isolated from the liquid substrate fermentation cultures of the mangrove endopytic fungus Aspergillus sp. ZJ-68. It potently inhibited α-glucosidase, with an IC50 value of 12.4 µM [34]. A new furanone derivative, butanolide A (74), was isolated from the Antarctic marine-derived fungus Penicillium sp. S-1–18. It showed moderate PTP1B inhibitory activity, with an IC50 value of 27.4 μM [35]. Three known secondary metabolites, funalenone (75), aurasperone F (76), and fonsecin (77), were isolated from a marine-derived fungal strain Aspergillus sp. SF5929. These compounds inhibited PTP1B, with IC50 values ranging from 3.3 to 7.9 mM [36]. A new polyhydroxy p-terphenyl, asperterphenyllin A (78), was isolated from an endophytic fungus Aspergillus candidus LDJ-5. This compound inhibited PTP1B, with an IC50 value of 21µM [37].
The fermented extract of marine-derived fungal strain Penicillium spp. and Eurotium sp. yielded a compound, flavoglaucin (79), which inhibited PTP1B activity, with an IC50 value of 13.4 µM [38]. A bioassay-guided investigation of the methylethylketone extract of the marine-derived fungus Penicillium sp. JF-55 cultures led to the isolation of a new PTP1B-inhibitory styrylpyrone-type metabolite, penstyrylpyrone (80), and a known metabolite, anhydrofulvic acid (81). Both compounds inhibited PTP1B activity in a dose-dependent manner [39]. A chemical investigation of the marine-derived fungal strain Penicillium glabrum SF-7123 revealed two known secondary fungal metabolites, myxotrichin C (82) and deoxyfunicone (83). Compound 82 inhibited PTP1B, with an IC50 value of 19.2 µM, and compound 83 inhibited PTP1B, with an IC50 value of 24.3 µM [40]. Investigation of a marine-derived fungus Penicillium sp. SF-6013 led to the discovery of two known analogs, tanzawaic acids A (84) and B (85), which significantly inhibited PTP1B activity, with the same IC50 value of 8.2 µM [41]. A known prenylated flavanone derivative (86) from the culture broth of an Indonesian marine sponge-derived Cladosporium sp. TPU1507 inhibited PTP1B, with an IC50 value of 11 μM [42]. During a bioassay-guided study on the EtOAc extract of a marine-derived fungus Cosmospora sp. SF-5060, aquastatin A (87) was isolated as a PTP1B-inhibitory component, with an IC50 value of 0.19 µM [43]. Two new 3,4,6-trisubstituted α-pyrone derivatives, chrysopyrones A and B (88 and 89), isolated from Penicillium chrysogenum SCSIO 07007, inhibited PTP1B, with IC50 values of 9.32 and 27.8 μg/mL, respectively [44]. A new γ-pyrone-containing polyketide, fusaresters B (90), isolated from a marine-derived fungus Fusarium sp. Hungcl, had a PTP1B inhibition rate of 56% at 40 μM [45]. Linoleic acid (91), identified from the marine fungus Eutypella sp. F0219, enhanced mitochondrial oxidation through the FABP4 axis [46].
Through statistical analysis, 91 polyketones were successfully isolated from 36 strains of marine-derived fungi. These compounds were found to display biological activity against diabetes-related enzymes. The structure is presented in Figure 2 below.

2.2. Alkaloid

Alkaloids, nitrogen-containing organic compounds, are ubiquitously present in nature. They are predominantly found in plants but also exist in animals and microorganisms. Their intricate structures, typically featuring nitrogen-atom-based rings, give rise to a wide variety of types [46]. Alkaloids possess significant biological activities and medicinal value. For instance, morphine is used for pain relief, quinine for malaria treatment, and caffeine stimulates the nervous system [47]. In agriculture, some alkaloids function as natural insecticides. Due to their unique properties, alkaloids are a focal point of research in drug development and natural product chemistry. Scientists explore biological resources to discover new alkaloids and study their mechanisms, aiming to develop better products for human health and agriculture.
Thiolactone (92) was isolated from Meira sp. 1210CH-42 and it inhibited α-glucosidase, with an IC50 value of 148.4 μM, outperforming acarbose (IC50 = 418.9 μM) [48]. A new tyrosine-derived metabolite, aspergillusol A (93), was isolated on a gram scale from the marine-derived fungus Aspergillus aculeatus CRI323-04. It selectively inhibited α-glucosidase from Saccharomyces cerevisiae but had no effect on the bacterial α-glucosidase from Bacillus stearothermophilus [49]. By feeding tryptophan to the marine-derived fungus Aspergillus sp. HNMF114 sourced from the bivalve mollusk Sanguinolaria chinensis, two known quinazoline-containing indole alkaloids, lapatin A (94) and scequinadoline E (95), were obtained. Both compounds inhibited α-glucosidase, with IC50 values of 7.18 and 5.29 mM, respectively [50]. Two new sambutoxin derivatives, sambutoxin A (96) and sambutoxin B (97), along with three known sambutoxin derivatives, (–)-sambutoxin (98), ilicicolin H (99), and deoxyleporin B (100), were isolated from the semimangrove endophytic fungus Talaromyces sp. CY-3. These compounds inhibited α-glucosidase, with IC50 values ranging from 12.6 ± 0.9 to 57.3 ± 1.3 μM, outperforming the positive control 1-deoxynojirimycin (IC50 = 80.8 ± 0.3 μM). Molecular docking analysis indicated that the activity potencies of compounds 96–98 correlated with the number of hydrogen bonds formed with α-glucosidase [51]. A new lumazine peptide, penilumamide K (101), was isolated from the deep-sea-derived fungus Aspergillus sp. SCSIO 41029. It showed significant inhibitory activity against α-glucosidase, with an IC50 value of 18.61 μΜ [52]. A new indole-diterpenoid, penpaxilloids A (102), along with the known compound paspalinine-13-ene (103), was isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Compound 102 inhibited protein tyrosine phosphatase 1B (PTP1B), with an IC50 value of 8.60 ± 0.53 μM, while compound 103 inhibited α-glucosidase, with an IC50 value of 19.96 ± 0.32 μM [53]. From a mangrove fungus Mycosphaerella sp. SYSU-DZG01, a new metabolite, asperchalasine I (104), and a known compound, asperchalasine A (105), were isolated. Both compounds inhibited α-glucosidase, with IC50 values of 17.1 and 15.7 μM, respectively [24]. Two undescribed 4-quinolone alkaloids, (±)-oxypenicinolines A (106–107), and a known analog quinolactacide (108), were isolated from the mangrove-derived fungus Penicillium steckii SCSIO 41025. (±)-Oxypenicinoline A (106–107) and quinolactacide (108) inhibited α-glucosidase, with IC50 values of 317.8 and 365.9 μΜ, respectively, which were more potent than acarbose (461.0 μM) [54].
Chemical investigation of P. brefeldianum F4a led to the discovery of two known compounds, riboflavin (109) and indole-3-acetic acid (110). Compounds 109 and 110 showed PTP1B inhibitory activity, with IC50 values of 8.87 and 11.68 μM, respectively, and compound 110 also inhibited α-glycosidase, with an IC50 value of 21.48 μM [31]. Two new compounds, epipaxilline (111) and penerpene J (112), were isolated from the marine-derived fungus Penicillium sp. KFD28. They inhibited PTP1B, with IC50 values of 31.5 and 9.5 μM, respectively [55]. Three new indole-diterpenoids, penerpene O (113), penerpene P (114), and penerpene U (115), and a known analog, dehydroxypaxilline (116), were isolated from the marine soft coral-derived fungus Aspergillus sp. ZF-104. Compounds 113–116 inhibited PTP1B, with IC50 values ranging from 14.3 to 28.1 μM, comparable to that of the positive control NaVO₃ (IC50 = 33.6 μM) [56]. A known compound, emethacin C (117), was obtained from the marine-derived fungus Aspergillus terreus RA2905. It inhibited PTP1B, with an IC50 value of 12.25 μM [57]. Malformin A1 (118), a known secondary metabolite, was isolated from a marine-derived fungal strain Aspergillus sp. SF5929. It inhibited PTP1B, with an IC50 value of 5.2 ± 0.5 μM [36]. Bioassay-guided investigation of organic extracts from several marine-derived fungal species led to the isolation of fructigenine A (119), cyclopenol (120), echinulin (121), and viridicatol (122). These compounds inhibited PTP1B, with IC50 values of 10.7, 30.0, 29.4, and 64.0 μM, respectively [38]. Cladosporamide A (123) isolated from the culture broth of an Indonesian marine sponge-derived Cladosporium sp. TPU1507 inhibited PTP1B, with an IC50 value of 48 μM [42]. Penicopeptide A (124) was isolated from the deep-sea-derived Penicillium solitum MCCC 3A00215. It binds directly to GSK-3β (KD = 177 nM), activating its phosphorylation and leading to β-catenin accumulation [58]. A new disubstituted maleimide, aspergteroid G (125), was isolated from the fermentation extract of the soft-coral-associated symbiotic and epiphytic fungus Aspergillus terreus EGF7-0-1. It is suppressed by glycogen synthase kinase-3 beta (GSK-3β) [59]. A new isopyrrolonaphthoquinone (126) was isolated from the fungal Biscogniauxia mediterranea LF657, which was from the Herodotes Deep (2800 m depth) in the Mediterranean Sea. It inhibited glycogen synthase kinase (GSK-3β), with an IC50 value of 8.04 μM [60]. A new fumiquinazoline alkaloid, scequinadoline D (127), was isolated and characterized from the marine fungus Scedosporium apiospermum F41-1. It acts through activation of the PPARγ pathway, stimulating the mRNA expression of FABP4 [61].
Upon statistical analysis, 36 alkaloids were successfully isolated from 15 strains of marine-derived fungi. These compounds demonstrated biological activity against diabetes-related enzymes. The structure is presented in Figure 3 below.

2.3. Terpenoids

Terpenoids, which are natural organic compounds widely distributed in nature, are composed of linked isoprene units that form a distinctive molecular framework, contributing to their rich structural diversity. Based on the number of isoprene units, they can be classified into monoterpenes, sesquiterpenes, diterpenes, and so on. These compounds mainly originate from plants, and some are also synthesized by microorganisms and marine organisms. Terpenoids have diverse bio-activities, such as anti-inflammatory, antibacterial, and anti-tumor effects [62]. Notably, they hold promise in diabetes prevention and treatment by regulating insulin secretion and improving insulin resistance. They also find applications in the spice industry and agriculture. Given their unique features and broad prospects, terpenoids are a research focus in multiple fields and are expected to contribute to diabetes drug R&D in the future.
Three new meroterpenoids, chrodrimanin O (128), chrodrimanin R (129), and chrodrimanin S (130), along with a known compound 131, were isolated from the fermentation broth of Penicillium sp. SCS-KFD09 sourced from the marine worm Sipunculus nudus collected in Haikou Bay, China. These compounds inhibited protein tyrosine phosphatase 1B (PTP1B), with IC50 values of 71.6, 62.5, 63.1, and 39.6 μM, respectively [63]. A new ∆8,9-steroid (132) and a known analog (133) were isolated from Meira sp. 1210CH-42. They inhibited α-glucosidase, with IC50 values of 86.0 and 279.7 μM, respectively, outperforming acarbose (IC50 = 418.9 μM) [48]. Chemical analysis of the EtOAc extract from the fermentation broth of the marine-derived fungus Trametes sp. ZYX-Z-16 led to the identification of two ergostane steroid analogs: ergosta-4,6,8,22E-tetraene-3-one (134) and 14α-hydroxyergosta-4,7,22E-triene-3,6-dione (135). These compounds inhibited the enzyme, with IC50 values of 104.1 and 111.3 μM, respectively, compared to the positive control acarbose (304.6 μM) [64]. A novel drimane sesquiterpene (136) was isolated from the marine-derived fungus Penicillium sp. TW58-16, showing strong α-glucosidase inhibitory effects, with inhibition rates of 35.4% at 400 μM [17]. Chemical investigation of the culture broth of P. levitum strain N33.2, extracted with ethyl acetate, led to the isolation of three ergostane-type steroid components: ergosterol peroxide (137) and (3β,5α,22E)-ergosta-6,8,22-triene-3,5-diol (138). Compounds 137 and 138 inhibited α-glucosidase, with IC50 values of 21.89 (51.14 μM equivalent) and 25.81 μg/mL (60.02 μM equivalent), respectively, more potently than acarbose (IC50 = 235.56 μg/mL) [65]. Demethylincisterol A2 (139), a known compound, was isolated from the soft-coral-derived fungus Aspergillus hiratsukae SCSIO 5Bn1003. It inhibited α-glucosidase, with an IC50 value of 35.73 μM, close to acarbose (IC50 = 32.92 μM) [66]. Study of the ethyl acetate extract from the deep-sea-derived fungus Penicillium thomii YPGA3 resulted in the isolation of known analogs austalide P (140) and a derivative agathic acid (141). Compounds 140 and 141 inhibited α-glucosidase, with IC50 values of 910 and 525 μM, respectively, more actively than the positive control acarbose (1.33 μM) [67].
GKK1032B (142), isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41512, inhibited protein tyrosine phosphatases PTP1B, with an IC50 value of 25 μM [68]. Four known analogs, ascomylactam B (143) and phomapyrrolidone A-C (144–146), were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. These compounds inhibited PTP1B, with IC50 values ranging from 8.7 to 11 μM [69]. A new compound 147 from the marine sponge-derived fungus Penicillium chrysogenum exhibited moderate activity against PTP1B at a concentration of 30 μM [70].
Chemical investigation of the marine-derived fungal isolate Penicillium sp. SF-5497 led to the isolation of a new preaustinoid-related meroterpenoid, preaustinoid A7 (148), along with a known metabolite (149). Both compounds inhibited PTP1B activity, with IC50 values of 17.6 and 58.4 μM, respectively, and compound 148 inhibited PTP1B in a noncompetitive manner [71]. Three novel indole-terpenoids, penerpene E (150), penerpene F (151), and penerpene H (152), along with a known compound 7-hydroxypaxilline-13-ene (153), were isolated from the marine-derived fungus Penicillium sp. KFD28. These compounds inhibited PTP1B, with IC50 values ranging from 13 to 27 μM [72]. Two unusual indole-terpenoids, penerpene A (154) and penerpene B (155), isolated from the same fungus, inhibited PTP1B with IC50 values of 1.7 and 2.4 μM, respectively [73]. A new merosesquiterpene, verruculide A (156), along with known congeners chrodrimanin A (157) and chrodrimanin H (158), was isolated from the culture broth of Indonesian ascidian-derived Penicillium verruculosum TPU1311. These compounds inhibited PTP1B, with IC50 values of 8.4, 8.5, and 14.9 μM, respectively [74].
Upon statistical analysis, 31 terpenoids were successfully isolated from 12 strains of marine-derived fungi. These compounds possess biological activity against diabetes-related enzymes. The structure is presented in Figure 4 below.

2.4. Lignan

Lignans, a class of natural organic compounds, are formed when two phenylpropanoid derivatives link via the β-carbon atoms of their side-chains. They have unique and diverse structures and are widely found in plants such as Schisandra chinensis and Forsythia suspensa [75]. Lignans exhibit diverse biological activities, particularly attracting attention in diabetes research. Some can inhibit α-glucosidase, while others enhance insulin sensitivity by regulating the insulin signaling pathway, and their antioxidant and anti-inflammatory properties are beneficial for countering diabetes-related oxidative stress and inflammation, holding promise for diabetes prevention and treatment.
Three new butenolide derivatives, flavipesolides A-C (159–161), were isolated alongside two known compounds, 5-[(3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-3-hydroxy-4-(4-hydroxyphenyl)-2(5H)furanone (162) and aspernolide A (163), from the marine-derived Aspergillus flavipes HN4-13 obtained from a Lianyungang coastal sediment sample. Compounds 159 to 161 inhibited α-glucosidase, with Ki/IC50 values of (2.5, 19)/44, (3.4, 14)/57, and (9.2, 4.7)/95 μM, respectively. Compounds 162 and 163 inhibited α-glucosidase non-competitively, with Ki/IC50 values of 0.43/34 and 2.1/37 μM, respectively. Compared to compound 161, esterified compounds 159 and 160 exhibited stronger α-glucosidase inhibitory activity [13]. Three new butenolide derivatives, (±)-asperteretal D (164–165) and asperteretal E (166), with a rare 2-benzyl-3-phenyl substituted lactone core, along with four known analogs, flavipesolide B (167), flavipesolide C (168), butyrolactone I (169), and 5-[(3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-3-hydroxy-4-(4-hydroxyphenyl)-2(5H)-furanone (170), were derived from Aspergillus terreus from the marine sponge Phakellia fusca. Compounds 164 to 170 potently inhibited α-glucosidase, with IC50 values ranging from 8.65 to 20.3 mM [76]. A new butenolide derivative, versicolactone G (171), was isolated from a coral-associated Aspergillus terreus. It inhibited α-glucosidase with a potent IC50 value of 104.8 ± 9.5 μM, lower than that of the positive control acarbose [77]. Four known compounds, butyroscavin (172), butyrolactone II (173), aspernolide D (174), and aspulvinone E (175), were obtained from the deep-sea-derived fungus Aspergillus sp. SCSIO 41029. They had significant α-glucosidase inhibitory potency, with IC50 values ranging from 18.61 to 109.06 μM [52].
Three known analogs, butyrolactone VII (176), aspernolide A (177), and aspernolide E (178), were isolated from the ethyl acetate extract of the deep-sea-derived Aspergillus terreus YPGA10. These compounds inhibited α-glucosidase, with IC50 values of 1.37, 6.98, and 8.06 μM respectively, much lower than that of the positive control acarbose [78]. Two known compounds, (+)-3′,3′-di-(dimethylallyl)-butyrolactone II (179) and 3-hydroxy-5-(4-hydroxybenzyl)-4-(4-hydroxyphenyl)furan-2(5H)-one (180), were isolated from Aspergillus terreus SCAU011 in the rhizosphere sediment of the mangrove plant Rhizophora stylosa. Compounds 179 and 180 inhibited α-glucosidase, with IC50 values of 56.1 and 12.9 μM, respectively [79]. A racemate of a novel diphenolic derivative, (±)-tylopilusin D (181), was isolated from the marine-derived fungal strain Aspergillus sp. SF5929. It inhibited PTP1B activity, with an IC50 value ranging from 8.1 ± 0.4 mM [36].
After statistical analysis, 23 lignans were successfully isolated from six strains of marine-derived fungi. These compounds were determined to possess biological activity against diabetes-related enzymes. The structure is presented in Figure 5 below.
Table 1. Enzyme activity of compounds associated with diabetes.
Table 1. Enzyme activity of compounds associated with diabetes.
Compound
Number		Derived FungiSampling SourceActivity-Related
Enzyme		Reference
1–5Aspergillus flavipes HN4-13Lianyungang coastal sediment sampleα-glucosidase[13]
159–163
6–8Alternaria alternata LW37a deep-sea sediment sample collected at a depth of 2623 m in the Southwest Indian Ridgeα-glucosidase[14]
9–13Penicillium thomii YPGA3the sediments of the Yap Trenchα-glucosidase[15]
14–19Aspergillus insulicoladeep-sea sediments, which were collected from the South China Sea at a depth of 2500 m.α-glucosidase[16]
20–26Penicillium sp. TW58-16hydrothermal vent sediment, collected from Kueishantao, Taiwanα-glucosidase[17]
136
27–29Aspergillus candidus HM5-4sponges from the South China Seaα-glucosidase[18]
30–32Talaromyces indigoticus FS688the South China Sea (118°19.692′ N, 20°38.982′ E; depth 2372 m)α-glucosidase[19]
33–37Eurotium sp. SCSIO F452sediment samples from northern South China Seaα-glucosidase[20]
38–39Meira sp. 1210CH-42a seawater sample collected at the Chuuk Islands, Federated States of Micronesiaα-glucosidase[21]
40–42Trichoderma sp. 307the stem bark of Clerodendrum inerme, which was collected from Zhanjiang Mangrove National Nature Reserve in Guangdong Province, China.α-glucosidase[22]
43–45Daldinia eschscholtzii HJ004the mangrove Bruguiera sexangula var. Rhynchopetala collected in the South China Seaα-glucosidase[23]
46Mycosphaerella sp. SYSU-DZG01the fruit of the marine mangrove plant Bruguiera collected in 2014 in Hainan Dongzhai Harbor Mangrove Reserveα-glucosidase[24]
104–105
47–49Aspergillus sp. 16-5Bthe leaves of Sonneratia apetala, which was collected from Dongzhaigang Mangrove National Nature Reserve in Hainan Island, Chinaα-glucosidase[25]
50–52Penicillium pinophilum SCAU037the roots of a mangrove plant Rhizophora stylosa on the Techeng Isle, Chinaα-glucosidase[26]
53–56Aspergillus flavus QQSG-3a fresh branch of Kandelia obobata, which was collected from Huizhou city in the province of Guangdong, Chinaα-glucosidase[27]
57Penicillium strain M30the sediment that was collected at a depth of 14 m sea at the Co To island, Northern Vietnamα-glucosidase[28]
58Aspergillus candidusthe gorgonian coral Anthogorgia ochracea collected from the South China Seaα-glucosidase[29]
59–60Daldinia eschscholtzii HJ004the stem of mangrove Brguiera sexangula var. rhynchopetala, collected in the South China Seaα-glucosidase[30]
61Penicillium brefeldianum F4athe roots of H. cordataα-glucosidase and PTP1B[31]
109α-glucosidase
110α-glucosidase and PTP1B
62–63Trichoderma sp. 307the stem bark of Clerodendrum inerme, collected in Zhanjiang Mangrove National Nature Reserve in Guangdong Province, Chinaα-glucosidase[32]
64–72Penicillium chrysogenum SCSIO 41001the deep sea sediment of Indian Ocean (Lat: 10.00371667° N, long: 88.72803333° E) at a depth of 3386 mα-glucosidase[33]
73Aspergillus sp. ZJ-68fresh leaves of the mangrove plant Kandelia candel, which were collected from the Zhanjiang Mangrove Nature Reserve in Guangdong Province, Chinaα-glucosidase[34]
74Penicillium sp. S-1-18the Antarctic seabed sediments (47.09° W, 62.05° S, the depth of 1393 m)PTP1B[35]
75–77Aspergillus sp. SF5929marine-derivedPTP1B[36]
118
181
78Aspergillus candidus LDJ-5the root of Rhizophora apiculata Blume in the Sanya Bailu Park of Hainan Province, ChinaPTP1B[37]
79Penicillium sp. SF-5203an intertidal sediment sample collected from Wan Island, KoreaPTP1B[38]
119–122
80–81Penicillium sp. JF-55an unidentified sponge that was manually collected using scuba equipment off the shores of Jeju IslandPTP1B[39]
82–83Penicillium glabrum SF-7123sediments that were collected using a dredge at the Ross Sea (77°34.397′ N, 166°10.865′ W)PTP1B[40]
84–85Penicillium sp. SF-6013the sea urchin Brisaster latifrons collected from the Sea of Okhotsk (N 53°22.626′ E 144°24.200′)PTP1B[41]
86Cladosporium sp. TPU1507an unidentified marine sponge collected at Manado, IndonesiaPTP1B[42]
123
87Cosmospora sp. SF-5060an inter-tidal sediment collected at Gejae IslandPTP1B[43]
88–89Penicillium chrysogenum SCSIO 07007deep-sea hydrothermal vent environment sample collected from the Western AtlanticPTP1B[44]
90Fusarium sp. Hungclthe soil, collected from the Futian Mangrove Reserve in Shenzhen, Guangdong ProvincePTP1B[45]
91Eutypella sp. F0219a marine sediment sample collected in the northern part of the South China Sea (GPS 114.6609° E, 21.5942° N) at a water depth of 75 mFABP4[46]
92Meira sp. 1210CH-42a seawater sample collected at Chuuk Islands, Federated States of Micronesiaα-glucosidase[48]
132–133
93Aspergillus aculeatus CRI323-04the marine sponge Xestospongia testudinaria (specimen no. CRI323)α-glucosidase[49]
94–95Aspergillus sp. HNMF114the bivalve mollusk Sanguinolaria chinensisα-glucosidase[50]
96–100Talaromyces sp. CY-3the fresh leaves of the semimangrove Hibiscus tiliaceusα-glucosidase[51]
101Aspergillus sp. SCSIO 41029a deep-sea sediment sample of South China Seaα-glucosidase[52]
172–175
102Penicillium sp. ZYX-Z-143an arthropod, Dardanus scutellatus, collected from Yinyu Island, one of the Paracel Islands in South China Sea, Hainan province (16°35′03″ N, 111°42′39″ E)PTP1B[53]
103α-glucosidase
106–108Penicillium steckii SCSIO 41025the root of A. marina (Forsk.) Vierh. (Acanthaceae) collected from the mangrove wetland in Zhanjiang, Guangdong province, China (coordinates 21.235° N, 110.451° E)α-glucosidase[54]
111–112Penicillium sp. KFD28Meretrix lusoria, collected from Haikou Bay, ChinaPTP1B[55]
113–116Aspergillus sp. ZF-104a marine soft coral in Haikou Bay, Hainan province, ChinaPTP1B[56]
117Aspergillus terreus RA2905a piece of fresh tissue from the inner part of the sea hare Aplysia pulmonica, collected from the Weizhou coral reefs in the South China SeaPTP1B[57]
124Penicillium solitum MCCC 3A00215deep-sea-derivedGSK-3β[58]
125Aspergillus terreus EGF7-0-1soft coral in the South China SeaGSK-3β[59]
126Biscogniauxiathe sediment of the Herodotes Basin (2800 m water depth)GSK-3β[60]
127Scedosporium apiospermum F41-1the inner tissue of the soft coral Lobophytum crassum collected from Hainan Sanya National Coral Reef Reserve, People’s Republic of ChinaFABP4[61]
128–131Penicillium sp. SCS-KFD09a marine worm, Sipunculusnudus, from Haikou Bay, ChinaPTP1B[63]
134–135Trametes sp. ZYX-Z-16an unidentified sea snail collected from Silver Island, Xisha, South Sea, Chinaα-glucosidase[64]
137–138Penicillium levitum N33.2the leaf of seagrass Enhalus acoroides (Hydrocharitaceae, Alismatales) obtained at Nhatrang bay, Khanhhoa, Vietnam (N 12°59.243′, E 109°21.965′) and symbolized as N33.2.α-glucosidase[65]
139Aspergillus hiratsukae SCSIO 5Bn1003a coral sample collected from the South China Seaα-glucosidase[65]
140–141Penicillium thomii YPGA3deep sea water at a depth of 4500 m in the Yap Trench (West Pacific Ocean)α-glucosidase[67]
142Penicillium sp. SCSIO 41512a soft coral of the South China SeaPTP1B[68]
143–146Microascus sp. SCSIO 41821a gorgonian Melitodes squamata collected from the South China Sea, Sanya (18°11′ N, 109°25′ E), Hainan, ChinaPTP1B[69]
147Penicillium chrysogenumPlakortis simplex collected in Xisha islands, ChinaPTP1B[70]
148–149Penicillium sp. SF-5497a sample of sea sand collected at Gijang-gun, Busan (35°22.2257′ N; 129°23.9238′ E)PTP1B[71]
150–153Penicillium sp. KFD28a bivalve mollusk, Meretrix lusoria, collected from Haikou Bay, ChinaPTP1B[72]
154–155Penicillium sp. KFD28a bivalve mollusk, Meretrix lusoria, collected from Haikou Bay, ChinaPTP1B[73]
156–158Penicillium verruculosum TPU1311an ascidian Polycarpa aurata collected in IndonesiaPTP1B[74]
164–170Aspergillus terreusmarine-derivedα-glucosidase[76]
171Aspergillus terreusthe coral Sarcophyton subviride, which was collected from the coast of Xisha Island in the South China Seaα-glucosidase[77]
176–178Aspergillus terreus YPGA10the deep-sea water at a depth of 4159 m in the Yap Trench (West Pacific Ocean)α-glucosidase[78]
179–180Aspergillus terreus SCAU011the rhizosphere sediment of a mangrove plant Rhizophora stylosa collected on the Techeng Isle, Chinaα-glucosidase[79]

3. Discussion

Natural products, serving as a crucial reservoir of bioactive substances, harbor a vast array of active products with diverse functions. In our research on natural products derived from marine fungi, we zeroed in on their correlation with diabetes-related enzyme activity. A total of 181 natural products sourced from marine fungi and exhibiting diabetes-related enzyme activity were meticulously counted in this study, with the aim of delving deeper into their latent value in the realm of diabetes prevention and management.
The study findings revealed that among these 181 natural products, compounds associated with alpha-glycosidase constituted the largest proportion. This underscores the pivotal role these compounds play in modulating blood-sugar metabolism (Table 1). α-glycosidase inhibitors can effectively impede the digestion and absorption of carbohydrates, thus curbing the sharp increase in post-meal blood glucose levels. Compounds related to PTP1B ranked second. As a key negative regulator within the insulin signaling pathway, modulating the activity of PTP1B contributes to the alleviation of insulin resistance. Conversely, the quantity of compounds linked to GSK-3β and FABP4 was relatively scarce. Significantly, two compounds, 61 and 110, were found to be associated with both α-glycosidase and PTP1B. This implies that these natural products might exert multiple mechanisms of action in regulating the activity of diabetes-related enzymes, thereby furnishing novel insights for the development of drugs for treating diabetes (Figure 6).
The chart illustrates a diverse range of strain sources. Sediment, accounting for 30.30%, provides a nutrient-rich and complex environment that may be conducive to the growth of fungi associated with diabetes-related enzyme-active secondary metabolites. Plant sources, representing 19.70% of the total, may foster the production of potentially valuable secondary metabolites by fungi due to plant–fungus symbiotic relationships. Seawater, making up 10.61%, has a unique environment that could enable fungi to develop distinctive metabolic pathways, leading to the generation of relevant bioactive substances (Figure 6). Animal sources, corals, and sponges, each with their respective proportions, may induce the synthesis of specific secondary metabolites in fungi due to their specialized ecological settings. The “others” category, constituting 6.06%, also holds exploration potential. These diverse sources offer abundant resources for the discovery of fungal secondary metabolites with diabetes-related enzyme activities.
Marine fungal natural products show great potential in diabetes-related enzyme activity research, yet drug development based on them is scarce. This is mainly due to the late start of research after 2000. Compared with traditional drug R&D, the data and theoretical basis are weak, impeding the transition from basic research to drug development. Also, their low yield and difficult extraction cannot meet the sample needs for in-depth research, blocking the analysis of the interaction mechanism between active ingredients and diabetes-related enzymes. However, there is hope for the future. As research advances, more data will support drug development. Moreover, advanced technologies like genetic engineering and synthetic biology may precisely regulate marine fungal metabolic pathways, increase yields, and promote diabetes treatment drug R&D, bringing more hope to patients.

Author Contributions

Z.W. drafted the manuscript; M.Z. and Y.Y. collected the data; F.K. and Q.W. conceived, guided, and revised the manuscript; N.L. revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the 2024 Guangxi Master Graduate Innovation Program (YCSW2024278), Joint Program on Health Science & Technology Innovation of Hainan Province (WSJK2024MS171), Hainan Province Clinical Medical Center (QWYH202175), the Natural Science Foundation of China (82360699), the Talent Scientific Research Initiation Project of Guangxi Minzu University (2020KJQD09 and 2021KJQD09), and the Xiangsi Lake Youth Innovation Team Project of Guangxi Minzu University (2021RSCXSHQN01).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Conflicts of Interest

The authors declare no conflicts of interest.

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Marinedrugs 23 00142 g001
Figure 1. Proportions of compounds with different structures and fungal sources.
Figure 1. Proportions of compounds with different structures and fungal sources.
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Figure 2. Structure diagram of polyketones.
Figure 2. Structure diagram of polyketones.
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Figure 3. Alkaloid structure diagram.
Figure 3. Alkaloid structure diagram.
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Figure 4. Terpenoids diagram of terpenoids.
Figure 4. Terpenoids diagram of terpenoids.
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Figure 5. Lignan diagram of lignans.
Figure 5. Lignan diagram of lignans.
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Figure 6. Percentage distributions of compounds against different diabetes-related enzymes (left) and strain sources (right).
Figure 6. Percentage distributions of compounds against different diabetes-related enzymes (left) and strain sources (right).
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Wang, Z.; Zhao, M.; Yu, Y.; Kong, F.; Lin, N.; Wang, Q. Marine Fungal Metabolites as Potential Antidiabetic Agents: A Comprehensive Review of Their Structures and Enzyme Inhibitory Activities. Mar. Drugs 2025, 23, 142. https://doi.org/10.3390/md23040142

AMA Style

Wang Z, Zhao M, Yu Y, Kong F, Lin N, Wang Q. Marine Fungal Metabolites as Potential Antidiabetic Agents: A Comprehensive Review of Their Structures and Enzyme Inhibitory Activities. Marine Drugs. 2025; 23(4):142. https://doi.org/10.3390/md23040142

Chicago/Turabian Style

Wang, Zimin, Meirong Zhao, Yunxia Yu, Fandong Kong, Nanxin Lin, and Qi Wang. 2025. "Marine Fungal Metabolites as Potential Antidiabetic Agents: A Comprehensive Review of Their Structures and Enzyme Inhibitory Activities" Marine Drugs 23, no. 4: 142. https://doi.org/10.3390/md23040142

APA Style

Wang, Z., Zhao, M., Yu, Y., Kong, F., Lin, N., & Wang, Q. (2025). Marine Fungal Metabolites as Potential Antidiabetic Agents: A Comprehensive Review of Their Structures and Enzyme Inhibitory Activities. Marine Drugs, 23(4), 142. https://doi.org/10.3390/md23040142

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