Bioguided isolation of alternariol derivatives from Ficus-derived endophyte Alternaria alternata

Background: Endophytes are a rich source of bioactive natural products and suggested to contribute to the biological or defense activities of their host plants. Following our research on the discovery of bioactive metabolites from endophytes, Alternaria alternata was isolated from the leaves of Ficus carica L. fam Moraceae.

Materials and Methods: Large scale cultivation of the endophytic strain was carried out and the obtained extract was subjected to preliminary screening of antifungal and cytotoxic activities.

Results: Promising antifungal and cytotoxic activities were obtained for the extract. Bio-guided fractionation resulted in the isolation and identification of four alternariol derivatives (alternariol, alternariol-5-O-sulphate, alternariol-5-O-methyl ether, alternariol-5-O-methyl ether-4`-O-sulphate). The isolated compounds were tested for antifungal and cytotoxic effects. Results revealed highest antifungal activity for alternariol against A. terreus (MIC= 2.64 μg mL^-1) and F. oxysporum (MIC= 36 μg mL^-1) while alternariol-5-O-methyl ether exhibited the highest cytotoxicity against K-562 (CC₅₀= 3.72 μg mL^-1) and HUVEC (CC₅₀= 2.06 μg mL^-1) cell lines.

Conclusion: All alternariol derivatives showed potent cytotoxic and antifungal activities against A. terreus suggesting the contribution of this endophyte in the known antimicrobial and anticancer activities of the host plant.