Search Results (33)

Freshwater fungi have attracted considerable attention as a potential source of lead compounds with diverse and novel chemical structures and biological activities in drug discovery. This review summarizes 307 natural products of freshwater fungi from 1988 to the end of October 2025. These compounds are categorized into fourteen structural types, including fatty acids and their lactones (compounds 1–18), furans and furanones (compounds 19–31), pyrans and pyranones (compounds 32–109), benzoquinones, phenols and phenolic acids (compounds 110–141), naphthalenes and naphthalenones (compounds 142–192), authraquinones and xanthones (compounds 193–211, depsidones (compounds 212–217), macrolides (compounds 218–234), polyesters (compounds 235–237), alkaloids (compounds 238–251), peptides (compounds 252–280), terpenoids (compounds 281–300), steroids (compounds 301 and 302), and other compounds (compounds 303–307). Some of them displayed promising biological activity, mainly comprising antibacterial, cytotoxic, and nematicidal activities. The preliminary analysis of the Structure––Activity Relationship (SAR) of important compounds is also discussed. In the last section, current challenges and prospective research perspectives are briefly proposed based on opinions from previous reviews. This review would contribute to the understanding of the utilization and development of natural products derived from freshwater fungi as potent medical resources in the future. Full article

Background: Nanoparticles are a promise for wound-healing therapies. However, its lack of efficacy/safety represents a real challenge for therapeutic use. Objectives: To overcome these problems, the ethanolic extract of Casimiroa edulis leaves, previously reported for its anti-inflammatory, antibiotic, and antioxidant activities, was characterized by FIA-ESI-FTICR-MS and encapsulated in biodegradable nanoparticles for potential wound-healing therapies. Methods:Casimiroa edulis-loaded nanoparticles (CE-NP) were prepared using the rapid emulsion-diffusion method and characterized by their particle size distribution, molecular interactions, charge, morphology, pH, physical stability, and antioxidant and occlusive effects. Results: A total of 40/34 ions in positive/negative electrospray ionization modes were obtained from the extract exploration analysis and were putatively annotated by accurate mass against databases with an error tolerance ≤10 mDa. The most abundant compounds showed the following order: tetramethylscutellarein > rutin > S-usnate > lactose > eugenol derivative > rotenone. While polyphenols predominated, carbohydrates, depsidones/other phenolics, etc., were also detected. The solid/spherical nanoparticles observed by TEM were obtained with a blend of acetone:methyl ethyl ketone (75:25) as the organic phase, producing a unimodal particle size (169.30 ± 1.30 nm; PdI = 0.08 ± 0.03). The encapsulation/loading percentages were 57 ± 0.74/1.62 ± 0.02%, ensuring an entrapment of half the extract, as observed in the FTIR studies. The light backscatter profiles show minimal differences, indicating physical stability correlated with the Z potential (−9.45 ± 1.73 mV). The antioxidant activity of the extract/nanoparticles at 40 µg/mL was 17.27 ± 2.86/16.73 ± 1.28 μg/mL, two-fold higher than that previously reported for sapote seeds. Conclusions: Biodegradable CE-NP with suitable characteristics were obtained for the first time, representing a preliminary proposal for wound healing. Efficacy studies are required. Full article

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

Fungi are a prolific source of diverse bioactive metabolites, yet many remain unexplored. Among these, depsidones are a rare class of compounds with significant biological potential, but they are seldom reported in mushrooms. This study investigated the medicinal fungus Ganoderma lucidum, known for its extensive therapeutic use in traditional medicine. Fruiting bodies were extracted using petroleum ether, ethyl acetate, n-butanol, and methanol. Extracts were screened phytochemically and assessed for total phenolic content and antioxidant activity using the DPPH assay. Ethyl acetate extract exhibited the highest phenolic yield and antioxidant potential and was subsequently evaluated for cytotoxicity against HepG2, HCT116, MCF7, and A549 cancer cell lines. It showed notable anticancer activity with minimal toxicity to normal Vero cells. UHPLC/Q-TOF-MS/MS analysis of G. lucidum ethyl acetate extract tentatively identified nine minor depsidones including mollicellin G, simplicildone I, mollicellin B, talaromyone B, simplicildone A, purpactin C, emeguisin B, mollicellin E, and simplicildone D on the basis of high-resolution negative-mode detection and characteristic MS/MS fragmentation patterns. Molecular docking revealed strong binding affinities between these compounds and cancer-related targets (AKT1, CDK2, ERK1, TNFα), with simplicildone D and mollicellin G demonstrating particularly high interactions. These findings provide mechanistic insights into the observed bioactivity and highlight G. lucidum as a promising source of therapeutic depsidones for future anticancer drug development. Full article

Introduction: Antimicrobial resistance is a global threat, highlighting the urgent need for novel antimicrobial agents. Among the mechanisms of resistance, bacteria can release drug-degrading enzymes and express efflux pumps, as well as grow in protected aggregates known as biofilms. Pseudomonas aeruginosa and Staphylococcus aureus are among the most prevalent biofilm infections in chronic wounds, respiratory and urinary tract infections, and device-associated infections. Pseudocyphellaria faveolata (Delise) Malme is a lichen with metabolites with unexplored antimicrobial potential. Aims: To identify and characterize the major metabolites present in Pseudocyphellaria Faveolata and to determine their antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Methods: The molecules were purified by column chromatography and characterized by NMR spectroscopy. The antimicrobial activity of the compounds was determined in terms of proliferation, adhesion, and viability against P. aeruginosa and S. aureus by the broth microdilution method and crystal violet staining. Viability was determined by the resazurin reduction assay on normal human fibroblasts to determine cytotoxicity over human cells. Results: The major metabolites were spectroscopically characterized and identified as physciosporin and methyl virensate. Physciosporin showed antimicrobial activity on S. aureus, with a MIC of 32 μg/mL and MBC of 128 μg/mL, and prevented biofilm formation from 16 μg/mL. Methyl virensate also had antimicrobial activity on S. aureus (MIC = 64 μg/mL). None of these metabolites significantly affected P. aeruginosa proliferation, viability, or adhesion. Cytotoxicity of physciosporin at 16 ug/mL on normal human fibroblasts was below 20%. Conclusions: This is the first report on the study of the antimicrobial activity of these compounds. Physciosporin showed promising activity in preventing the formation of S. aureus biofilms, which are responsible for chronic infections. These findings provide a foundation for exploring the antimicrobial potential of other lichenic depsidones. Full article

Penicillide is the founder product of a class of natural products of fungal origin. Although this compound and its analogues have been identified from taxonomically heterogeneous fungi, they are most frequently and typically reported from the species of Talaromyces and Penicillium. The producing strains have been isolated in various ecological contexts, with a notable proportion of endophytes. The occurrence of penicillides in these plant associates may be indicative of a possible role in defensive mutualism based on their bioactive properties, which are also reviewed in this paper. The interesting finding of penicillides in fruits and seeds of Phyllanthus emblica is introductory to a new ground of investigation in view of assessing whether they are produced by the plant directly or as a result of the biosynthetic capacities of some endophytic associates. Full article

Various studies have shown that Hypogymnia physodes are a source of many biologically active compounds, including lichen acids. These lichen-specific compounds are characterized by antioxidant, antiproliferative, and antimicrobial properties, and they can be used in the cosmetic and pharmaceutical industries. The main aim of this study was to optimize the composition of natural deep eutectic solvents based on proline or betaine and lactic acid for the extraction of metabolites from H. physodes. The design of the experimental method and the response surface approach allowed the optimization of the extraction process of specific lichen metabolites. Based on preliminary research, a multivariate model of the experiment was developed. For optimization, the following parameters were employed in the experiment to confirm the model: a proline/lactic acid/water molar ratio of 1:2:2. Such a mixture allowed the efficient extraction of three depsidones (i.e., physodic acid, physodalic acid, 3-hydroyphysodic acid) and one depside (i.e., atranorin). The developed composition of the solvent mixtures ensured good efficiency when extracting the metabolites from the thallus of H. physodes with high antioxidant properties. Full article

Among female oncology patients, cervical cancer stands as the fourth most prevalent malignancy, exerting significant impacts on their health. Over 600,000 women received the diagnosis of cervical cancer in 2020, and the illness claimed over 300,000 lives globally. Curdepsidone A, a derivative of depsidone, was isolated from the secondary metabolites of Curvularia sp. IFB-Z10. In this study, we revised the molecular structure of curdepsidone A and investigated the fundamental mechanism of the anti-tumor activity of curdepsidone A in HeLa cells for the first time. The results demonstrated that curdepsidone A caused G0/G1 phase arrest, triggered apoptosis via a mitochondrial apoptotic pathway, blocked the autophagic flux, suppressed the PI3K/AKT pathway, and increased the accumulation of reactive oxygen species (ROS) in HeLa cells. Furthermore, the PI3K inhibitor (LY294002) promoted apoptosis induced by curdepsidone A, while the PI3K agonist (IGF-1) eliminated such an effect. ROS scavenger (NAC) reduced curdepsidone A-induced cell apoptosis and the suppression of autophagy and the PI3K/AKT pathway. In conclusion, our results revealed that curdepsidone A hindered cell growth by causing cell cycle arrest, and promoted cell apoptosis by inhibiting autophagy and the ROS-mediated PI3K/AKT pathway. This study provides a molecular basis for the development of curdepsidone A as a new chemotherapy drug for cervical cancer. Full article

Eleven new brominated depsidones, namely spiromastixones U-Z5 (1–11) along with five known analogues (12–16), were isolated from a deep-sea-derived fungus Spiromastix sp. through the addition of sodium bromide during fermentation. Their structures were elucidated by extensive analysis of the spectroscopic data including high-resolution MS and 1D and 2D NMR data. Compounds 6–10 and 16 exhibited significant inhibition against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) with MIC values ranging from 0.5 to 2.0 μM. Particularly, tribrominated 7 displayed the strongest activity against MRSA and VRE with a MIC of 0.5 and 1.0 μM, respectively, suggesting its potential for further development as a new antibacterial agent. Full article

The present study was intended for the identification of secondary metabolites in acetone extract of the lichen Hypotrachyna cirrhata using UPLC-ESI-QToF-MS/MS and the detection of bioactive compounds. This study led to the identification of 22 metabolites based on their MS/MS spectra, accurate molecular masses, molecular formula from a comparison of the literature database (DNP), and fragmentation patterns. In addition, potent antioxidant and α-glucosidase inhibitory potentials of acetone extract of H. cirrhata motivated us to isolate 10 metabolites, which were characterized as salazinic acid (11), norlobaridone (12), atranorin (13), lecanoric acid (14), lichesterinic acid (15), protolichesterinic acid (16), methyl hematommate (17), iso-rhizonic acid (18), atranol (19), and methylatratate (20) based on their spectral data. All these isolates were assessed for their free radicals scavenging, radical-induced DNA damage, and intestinal α-glucosidase inhibitory activities. The results indicated that norlobaridone (12), lecanoric acid (14), methyl hematommate (17), and atranol (19) showed potent antioxidant activity, while depsidones (salazinic acid (11), norlobaridone (12)) and a monophenolic compound (iso-rhizonic acid, (18)) displayed significant intestinal α-glucosidase inhibitory activities (p < 0.001), which is comparable to standard acarbose. These results were further correlated with molecular docking studies, which indicated that the alkyl chain of norlobaridione (12) is hooked into the finger-like cavity of the allosteric pocket; moreover, it also established Van der Waals interactions with hydrophobic residues of the allosteric pocket. Thus, the potency of norlobaridone to inhibit α-glucosidase enzyme might be associated with its allosteric binding. Also, MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energies of salazinic acid (11) and norlobaridone (12) were superior to acarbose and may have contributed to their high activity compared to acarbose. Full article

Lichens are unique organisms that exhibit a permanent symbiosis between fungi and algae or fungi and photosynthetic bacteria. Lichens have been found to produce biotechnologically valuable secondary metabolites. A handful of studies showed that tailoring enzymes such as cytochrome P450 monooxygenases (CYPs/P450s) play a key role in synthesizing these metabolites. Despite the critical role of P450s in the biosynthesis of secondary metabolites, the systematic analysis of P450s in lichens has yet to be reported. This study is aimed to address this research gap. A genome-wide analysis of P450s in five lichens from the fungal class Lecanoromycetes revealed the presence of 434 P450s that are grouped into 178 P450 families and 345 P450 subfamilies. The study indicated that none of the P450 families bloomed, and 15 P450 families were conserved in all five Lecanoromycetes. Lecanoromycetes have more P450s and higher P450 family diversity compared to Pezizomycetes. A total of 73 P450s were found to be part of secondary metabolite gene clusters, indicating their potential involvement in the biosynthesis of secondary metabolites. Annotation of P450s revealed that CYP682BG1 and CYP682BG2 from Cladonia grayi and Pseudevernia furfuracea (physodic acid chemotype) are involved in the synthesis of grayanic acid and physodic acid, CYP65FQ2 from Stereocaulon alpinum is involved in the synthesis of atranorin, and CYP6309A2 from Cladonia uncialis is involved in the synthesis of usnic acid. This study serves as a reference for future annotation of P450s in lichens. Full article

The lichen Cetraria islandica (L.) Ach. has been used in traditional and modern medicines for its many biological properties such as immunological, immunomodulating, antioxidant, antimicrobial, and anti-inflammatory activities. This species is gaining popularity in the market, with interest from many industries for selling as medicines, dietary supplements, and daily herbal drinks. This study profiled the morpho-anatomical features by light, fluorescence, and scanning electron microscopy; conducted an elemental analysis using energy-dispersive X-ray spectroscopy; and phytochemical analysis was performed using high-resolution mass spectrometry combined with a liquid chromatography system (LC-DAD-QToF) of C. islandica. In total, 37 compounds were identified and characterized based on comparisons with the literature data, retention times, and their mass fragmentation mechanism/s. The identified compounds were classified under five different classes, i.e., depsidones, depsides, dibenzofurans, aliphatic acids, and others that contain simple organic acids in majority. Two major compounds (fumaroprotocetraric acid and cetraric acid) were identified in the aqueous ethanolic and ethanolic extracts of C. islandica lichen. This detailed morpho-anatomical, EDS spectroscopy, and the developed LC-DAD-QToF approach for C. islandica will be important for correct species identification and can serve as a useful tool for taxonomical validation and chemical characterization. Additionally, chemical study of the extract of C. islandica led to isolation and structural elucidation of nine compounds, namely cetraric acid (1), 9′-(O-methyl)protocetraric acid (2), usnic acid (3), ergosterol peroxide (4), oleic acid (5), palmitic acid (6), stearic acid (7), sucrose (8), and arabinitol (9). Full article

The discovery of natural drug metabolites is a leading contributor to fulfilling the sustainable development goal of finding solutions to global health challenges. Depsidones are a class of polyketides that have been separated from lichens, fungi, sponges, and plants and possess various bioactivities, including cytotoxic, antimicrobial, antimalarial, antituberculosis, acetylcholinesterase and α-glucosidase inhibition, and anti-inflammatory effects. Endocannabinoid receptors (CB1 and CB2) are G-protein-coupled receptors (GPCRs), and their activation mediates many physiological processes. CB1 is the dominant subtype in the central nervous system, while CB2 is mainly expressed in the immune system. The two receptors exhibit high heterogeneity, making developing selective ligands a great challenge. Attempts to develop CB2 selective agonists for treating inflammatory diseases and neuropathic pain have not been successful due to the high homology of the binding sites of the CB receptors. In this work, 235 depsidones from various sources were investigated for the possibility of identifying CB2-selective agonists by performing multiple docking studies, including induced fit docking and Prime/molecular mechanics–generalized Born surface area (MM-GBSA) calculations to predict the binding mode and free energy. Simplicildone J (10), lobaric acid (110), mollicellin Q (101), garcinisidone E (215), mollicellin P (100), paucinervin Q (149), and boremexin C (161) had the highest binding scores (−12.134 kcal/mol, −11.944 kcal/mol, −11.479 kcal/mol, −11.394 kcal/mol, −11.322 kcal/mol, −11.305 kcal/mol, and −11.254 kcal/mol, respectively) when screened against the CB2 receptor (PDB ID: 6KPF). The molecular dynamic simulation was performed on the compounds with the highest binding scores. The computational outcomes show that garcinisidone E (215) and paucinervin Q (149) could be substantial candidates for CB2 receptor activation and warrant further in vivo and in vitro investigations. Full article

Dengue is a mosquito-borne flavivirus that causes 21,000 deaths annually. Depsides and depsidones of lichens have previously been reported to be antimicrobials. In this study, our objective was to identify lichen-derived depsides and depsidones as dengue virus inhibitors. The 18 depsides and depsidones of Usnea baileyi, Usnea aciculifera, Parmotrema dilatatum, and Parmotrema tsavoense were tested against dengue virus serotype 2. Two depsides and one depsidone inhibited dengue virus serotype 2 without any apparent cytotoxicity. Diffractaic acid, barbatic acid, and Parmosidone C were three active compounds further characterized for their efficacies (EC₅₀), cytotoxicities (CC₅₀), and selectivity index (SI; CC₅₀/EC₅₀). Their EC₅₀ (SI) values were 2.43 ± 0.19 (20.59), 0.91 ± 0.15 (13.33), and 17.42 ± 3.21 (8.95) μM, respectively. Diffractaic acid showed the highest selectivity index, and similar efficacies were also found in dengue serotypes 1–4, Zika, and chikungunya viruses. Cell-based studies revealed that the target was mainly in the late stage with replication and the formation of infectious particles. This report highlights that a lichen-derived diffractaic acid could become a mosquito-borne antiviral lead as its selectivity indices ranged from 8.07 to 20.59 with a proposed target at viral replication. Full article

Aspergillus unguis belongs to the Aspergillus section Nidulantes. This species is found in soils and organisms from marine environments, such as jellyfishes and sponges. The first chemical study reported in the literature dates from 1970, with depsidones nidulin (1), nornidulin (2), and unguinol (3) being the first isolated compounds. Fifty-two years since this first study, the isolation and characterization of ninety-seven (97) compounds have been reported. These compounds are from different classes, such as depsides, depsidones, phthalides, cyclopeptides, indanones, diarylethers, pyrones, benzoic acid derivatives, orcinol/orsenillate derivatives, and sesterpenoids. In terms of biological activities, the first studies on isolated compounds from A. unguis came only in the 1990s. Considering the tendency for antiparasitic and antibiotics to become ineffective against resistant microorganisms and larvae, A. unguis compounds have also been extensively investigated and some compounds are considered very promising. In addition to these larvicidal and antimicrobial activities, these compounds also show activity against cancer cell lines, animal growth promotion, antimalarial and antioxidant activities. Despite the diversity of these compounds and reported biological activities, A. unguis remains an interesting target for studies on metabolic induction to produce new compounds, the determination of new biological activities, medicinal chemistry, structural modification, biotechnological approaches, and molecular modeling, which have yet to be extensively explored. Full article