Cryptosphaerolide, a Cytotoxic Mcl-1 Inhibitor from a Marine-Derived Ascomycete Related to the Genus Cryptosphaeria

Examination of the saline fermentation products from the marine-derived ascomycete fungal strain CNL-523 (Cryptosphaeria sp.) resulted in the isolation of cryptosphaerolide (1). The new compound is an ester-substituted sesquiterpenoid related to the eremophilane class, The structure of the new compound was assigned by spectroscopic and chemical methods. Cryptosphaerolide was found to be an inhibitor of the protein Mcl-1, a cancer drug target involved in apoptosis. It also showed significant cytotoxicity against an HCT-116 human colon carcinoma cell line, indicating that the compound may be of value in exploring the Mcl-1 pathway as a target for cancer chemotherapy.