In vitro cytotoxicity and secondary metabolites of Talaromyces wortmannii isolated from Arundo donax L. Identification of a new phytoceramide

Cancer remains a major global health threat, with breast, liver, and lung cancers showing particularly high incidence and mortality rates. Plant endophytes offer a unique resource for drug discovery. They produce bioactive compounds that may even surpass those of their host plants, providing a sustainable resource for new drugs. Herein, the in vitro cytotoxicity and secondary metabolites of the extract of white bean culture (EWBC) of the fungal endophyte, Talaromyces wortmannii isolated from Arundo donax L., a common reed grass were investigated. This led to the identification of a novel phytoceramide, namely talaroceramide (1), alongside other known structures, including stigmasterol (2), stigmasterol glucoside (5), thymine (3), and uracil (4). The EWBC extract exhibited cytotoxic effects on MCF7, HepG2, and A549 cancer cell lines, with IC₅₀ values of 54.57, 57.12, and 84.33 µg/mL, respectively. The EWBC extract demonstrated favorable selectivity indices ranging from 1.4 to 2.1 against the normal lung cell line (WI38), indicating selective cytotoxicity toward cancer cells over normal cells. The cytotoxicity observed, combined with the acceptable selectivity indices suggested the endophyte, T. wortmannii as a potential source for cytotoxic compounds. A docking study against Bcl-2 as a potential target for the discovery of anticancer drugs revealed that the new ceramide (1) showed the greatest binding affinity (-8.7894 kcal.mol^-1) and the best binding interactions amongst the identified compounds. Further research is suggested to validate the anticancer activity of the identified compounds.