Secondary metabolites of fungus Thyronectria sp. and their antifungal and anticancer activities

The genus Thyronectria belonging to the Nectriaceae family is predominantly characterized by perithecia covered with yellow scurf, whereas after drying its upper part, it usually becomes cupulate. The identified species of this genus (32 species) are rarely pathogenic, and are generally distributed in subtropical and temperate areas, growing on dead branches. So far there is no report on a chemical profile or biological activities of this genus [1]. This study aimed to isolate and identify secondary metabolites from a solid culture of Thyronectaria sp. on breakfast cereals, as well as to evaluate their antifungal and anticancer properties. Our bioprospecting using bioactivity guided isolation led to purification of a known halogenated heat shock protein 90 inhibitor radicicol (1) [2], two known cleistanthane type diterpenes (2 and 3), zythiostromic acid A and zythiostromic acid B, along with a new dimeric cleistanthane diterpene (4), for the first time from a solid culture of Thyronectria sp. Structures of all isolates were established using 1&2D NMR and HRMS. The absolute configuration of 1 and 4 were deciphered using X-Ray crystallography. Furthermore, concentration-dependent investigations for their cytotoxic activity against a melanoma cancer cell line (A375), and antifungal activity against Cryptococcus neoformans and Candida albicans revealed compounds 4 and 1 to be responsible respectively for the bioactivities observed. Our results demonstrated that Thyronectria sp. investigated in this work is a potential source of bioactive compounds and requires further in-depth investigations.