Altersteroids A–D, 9,11-Secosteroid-Derived γ-Lactones from an <i>Alternaria</i> sp.
Peinan Fu, Yang Zhang, Chenyin Wang, Shuyi Si, Xingzhong Liu, Yongsheng Che
Abstract
Altersteroids A–D ( 1 – 4 ), four new 9,11-secosteroid-derived γ-lactones, were isolated from cultures of the ascomycete fungus Alternaria sp. Their structures were elucidated primarily by NMR experiments. The absolute configuration of 1 was established by X-ray crystallographic analysis of its di- p -nitrobenzenesulfonate 1a using Cu Kα radiation, whereas those for 2 – 4 were assigned by quantum-chemical calculations. Compounds 1 – 4 incorporate a γ-lactone moiety fused to the steroid D ring at C-13/C-14. Compound 3 showed moderate cytotoxicity toward four tumor cell lines and induced an apoptotic process in A549 cells. Notably, compound 3 showed equipotent activity against the cisplatin-sensitive MB49 and -resistant MB49 CisR cells, with an IC 50 value of 12.7 μM.