Rare Sesterterpenoids from the Soil Derived Fungus, Aspergillus variecolor Strain SDG, Therapeutic Potential of Stellatic Acid and Docking Studies.

Ethyl acetate extract of the cultures of the soil-derived filamentous fungus, Aspergillus variecolor SDG strain from Nallamala forest resulted in the isolation of extremely rare sesterterpenoids, stellatic acid (1) and andilesin C (2). We report a thorough chemical characterization of these compounds using various spectroscopic techniques and evaluation of their in vitro preclinical therapeutic potential. Stellatic acid exhibits potent antioxidant activity with an IC50 of 38 µg/mL and significant anticancer activity against HeLa, HepG2, MCF7, and A549 cancer cell lines with an IC50 of 7-12 µM. On the other hand, andilesin C displayed moderate cytotoxicity against DU145 and B16F10 cancer cell lines but lacked antioxidant activity. Furthermore, the potential hypoglycemic property of stellatic acid was evaluated by measuring its inhibitory effect against α-glucosidase. It exhibited tenfold potency against yeast  α-glucosidase (IC50 101.73 µg/mL) than mammalian α-glucosidase (IC50 1000.00 µg/mL). Docking studies were also performed to suggest the interaction mode of stellatic acid in the α-glucosidase enzyme active site. Notably, yeast α-glucosidase shows a higher affinity towards stellatic acid than mammalian α-glucosidase (3TOP). Thus, the in vitro preclinical study of stellatic acid suggests its potential efficacy in therapeutic drug development.