Altersteroids A–D, 9,11-Secosteroid-Derived γ-Lactones from an <i>Alternaria</i> sp.

Abstract

Altersteroids A-D (<b>1</b>-<b>4</b>), four new 9,11-secosteroid-derived γ-lactones, were isolated from cultures of the ascomycete fungus <i>Alternaria</i> sp. Their structures were elucidated primarily by NMR experiments. The absolute configuration of <b>1</b> was established by X-ray crystallographic analysis of its di-<i>p</i>-nitrobenzenesulfonate <b>1a</b> using Cu Kα radiation, whereas those for <b>2</b>-<b>4</b> were assigned by quantum-chemical calculations. Compounds <b>1</b>-<b>4</b> incorporate a γ-lactone moiety fused to the steroid D ring at C-13/C-14. Compound <b>3</b> showed moderate cytotoxicity toward four tumor cell lines and induced an apoptotic process in A549 cells. Notably, compound <b>3</b> showed equipotent activity against the cisplatin-sensitive MB49 and -resistant MB49 CisR cells, with an IC₅₀ value of 12.7 μM.