Abstract
Fungi are recognized as luxuriant metabolic artists that generate propitious biometabolites. Historically, fungal metabolites have largely been investigated as leads for various therapeutic agents. Chaetomugilins and the closely related chaetoviridins are fungal metabolites, and each has an oxygenated bicyclic pyranoquinone core. They are mainly produced by various Chaetomaceae species. These metabolites display unique chemical features and diversified bioactivities. The current review gives an overview of research about fungal chaetomugilins and chaetoviridins regarding their structures, separation, characterization, biosynthesis, and bioactivities. Additionally, their antiviral potential towards the SARS-CoV-2 protease was evaluated using docking studies and molecular dynamics (MD) simulations. We report on the docking and predictive binding energy estimations using reported crystal structures of the main protease (PDB ID: 6M2N, 6W81, and 7K0f) at variable resolutions—i.e., 2.20, 1.55, and 1.65 Å, respectively. Chaetovirdin D (43) exhibited highly negative docking scores of −7.944, −8.141, and −6.615 kcal/mol, when complexed with 6M2N, 6W81, and 7K0f, respectively. The reference inhibitors exhibited the following scores: −5.377, −6.995, and −8.159 kcal/mol, when complexed with 6M2N, 6W81, and 7K0f, respectively. By using molecular dynamics simulations, chaetovirdin D’s stability in complexes with the viral protease was analyzed, and it was found to be stable over the course of 100 ns.
Highlights
Fungi are a wealthy and substantial pool of many secondary metabolites with many different structures and diversified bioactivities [1,2,3,4,5,6,7,8,9,10,11]
Chaetomugiline P (24) differs from the others in that it has no substituent at C-7 and a methyl group at C-5. 3-Methyl-4-hydroxy-1-pentyl chains at C-3 are found in some chaetomugilins and chaetoviridins
The current review focuses on chaetomugilins and chaetoviridins from fungal sources, including isolation, structural characterization, biosynthesis, and bioactivities (Tables 1 and 2)
Summary
Fungi are a wealthy and substantial pool of many secondary metabolites with many different structures and diversified bioactivities [1,2,3,4,5,6,7,8,9,10,11]. Yamada et al reported the isolation of chaetomugilins A (2), B (6), C (7), D (8), E (11), F (13), G (14), and H (15) from the culture broth of C. globosum associated with marine fish Mugil cephalus and assessed for their cytotoxic effects on P388 and HL-60 cell lines in the MTT assay (Figures 2 and 3; Table 2). C. globosum OUPS-T106B-6 isolated from M. cephalus yielded two new metabolites that demonstrated moderate cytotoxicity towards HL-60 and P388 cell lines (IC50 ranged from 10.3 to 24.1 μM, respectively), compared to 5-FU (IC50 2.7 and 1.7 μM) in the MTT assay [41]: chaetomugilins G (14) and H (15). The new metabolites, 11- and 4’-epichaetomugilin A (4 and 5) purified from C. globosum isolated from M. cephalus, displayed moderate to weak cytotoxicity toward KB, P388, HL-60, and L1210 cell lines [35]. Chaetovirdin E (5 μg/mL) exhibited cytotoxicity towards CaCO2 and HepG2 cancers cells with 30% and 59% inhibition, respectively [49]
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