Beyond Monomers: Discovery of Bioactive Naphthoquinone Heterodimers and Perenniporides from Pyrenochaetopsis Species

Abstract

Naphthoquinones can be found in Nature in various formats, both as standalone molecules and as building blocks for larger structures. A study of the fungus, Pyrenochaetopsis sp. (strain MSX63699), led to the isolation of naphthoquinone analogues (1-21), including both monomers and heterodimers and seven new compounds─three kirschsteinin analogues (11-13) and four perenniporides (18-21). The structures of these were elucidated through analysis of data from 1D and 2D NMR, HRESIMS, and ECD experiments, and several compounds displayed cytotoxic activity against melanoma (MDA-MB-435) and ovarian (OVCAR3) cancer cell lines, with structure–activity trends suggesting key roles for specific substituents in enhancing bioactivity. Notably, compounds 3-6, 9, 11, 15, and 19–20 had IC50 values that ranged from about 1 to 5 μM against both cell lines. Overall, this work expands the chemical diversity of fungal naphthoquinones by identifying new heterodimeric and perenniporide-type analogues and underscores the untapped biosynthetic potential of the Pyrenochaetopsis species.