Isochromophilones A–F, Cytotoxic Chloroazaphilones from the Marine Mangrove Endophytic Fungus <i>Diaporthe</i> sp. SCSIO 41011

Abstract

Six new highly oxygenated chloroazaphilone derivatives, isochromophilones A-F (1-6), were obtained from the mangrove-derived fungus Diaporthe sp. SCSIO 41011, together with six known analogues (7-12). The structures of 1-6 including absolute configurations were determined by detailed NMR, MS spectroscopic analyses, and electronic circular dichroism spectra. Compounds 1 and 2 represent the first reported azaphilones lacking a carbonyl group at C-6. Compound 8 exhibited cytotoxic activities against three renal carcinoma cell lines, ACHN, OS-RC-2, and 786-O cells, with IC₅₀ values ranging from 3.0 to 4.4 μM, and 4 showed activity against 786-O cells with an IC₅₀ of 8.9 μM. Further studies indicated that 4 induced apoptosis in 786-O cells in a dose- and time-dependent manner.