Bioactive metabolites from endophytes of African club moss- Selaginella kraussiana (Kunze) A. Braun exhibit broad-spectrum pharmaceutical utilities

• Published in: South African journal of botany 2024-06, Vol.169, p.301-313
• Main Authors: Santra, Hiran Kanti, Banerjee, Debdulal
• Format: Article
• Language: English
• Subjects: Antimicrobial; Antioxidative; Bioactive metabolites; Endophyte; S. kraussiana
• ISSN: 0254-6299; 1727-9321
• DOI: 10.1016/j.sajb.2024.04.039

•Endophytic fungi- Ascochyta medicaginicola SK16, Phoma sp. SK5 has been isolated from African Club moss- S. kraussiana (Kunze) A., collected from Darjeeling Himalayan hills.•Ethyl acetate (EA) extract of secondary metabolites of SK16 exhibited broad spectrum microbicidal activity against seventeen pathogens including Methicillin-resistant Staphylococcus aureus (MRSA), and C. albicans.•It inhibited pathogens’ key metabolic enzymes, caused leakage of major macromolecules, act synergistically with antibiotics/antifungals, blocked biofilm formation, and also stopped the yeast to hyphal transition in case C. albicans.•EA extracts of SK5 exhibited free radical scavenging activity against DPPH, ABTS, and H2O2, in-vitro antioxidative activity towards peritoneal macrophage cells, and also were cytotoxic against cancer cell lines.•Bioactive compounds were recorded by GC-MS analysis. The search for potent natural compounds from plant and microbial sources is increasing logarithmically to combat various types of health issues of which multidrug-resistant microbes and problems related to oxidative stress are the prime ones. Novel secondary metabolites from endophytes have always been potent alternatives to contemporary antimicrobials and antioxidants. The present study shows that two potent endophytic fungal isolates Ascochyta medicaginicola SK16 and Phomopsis sp. SK5 synthesises non-proteinaceous, thermostable secondary metabolites with broad-spectrum antimicrobial, antioxidative, and cytotoxic activity. Bioassay-guided fractionation revealed that the Ethyl acetate (EA) extract of the cell-free culture extract (CFCE) of SK5 and SK16 constitutes ten and eleven secondary metabolites of which 2,4, -di tert butyl phenol, aziridine- 1,2-amino ethyl, actinobolin, bactobolin, azulene, menthyl acetate, phenol, p-[2-(methylamino)ethyl], and imidazole components were significant. SK16 exhibited strong antimicrobial activity against seventeen pathogens including Methicillin-resistant Staphylococcus aureus (MRSA), and C. albicans with a minimum microbicidal concentration of 100- 400 µg mL−1. These metabolites disrupt the microbial cell membranes causing lethal leakage of biomacromolecules- nucleic acid, protein, and potassium ions. Enzymes involved in the EMP pathway, TCA cycle, and gluconeogenesis were also blocked. Both the biofilm formation and transition of Candida cells from the yeast-to-hyphal form were inhibited. SK5 metabolites are potent radical scavengers with an IC50