Phialomustin A–D, new antimicrobial and cytotoxic metabolites from an endophytic fungus, Phialophora mustea

Abstract

Phialomustin A–D (1–4), four new bioactive metabolites, with an unprecedented azaphilone derived skeleton, were isolated and characterized from an endophytic fungus isolated from Crocus sativus. The ITS-5.8S-ITS2 ribosomal gene sequence of the endophyte displayed a sequence similarity of more than 99% with Phialophora mustea. The structural determinations of compounds (1–4) were authenticated by spectroscopic and chemical analysis. The absolute configuration of the stereogenic centers of 1, 3 and 4 were determined by electronic circular dichroism spectroscopy. Compounds 3 and 4 showed promising antifungal activities against Candida albicans, with IC₅₀ values of 14.3 and 73.6 μM, whereas compound 2 exhibited remarkable cytotoxic activity against the human breast cancer cell line, T47D, with an IC₅₀ of 1 μM.