Exploring the Three-Dimensional Structures and Activity Relationships of N-Methyl and N-Desmethyl Analogues of Cyclodepsipeptide Destruxin E

Destruxin E was isolated from Metarhidium anisopliae in 1989 based on insecticidal activity along with other derivatives [Phytochemistry, 1981, 20, 715-723.].It inhibits V-ATPase at the IC50 value of 0.40 M, which is the most potent among destruxin derivatives [Chem.Biodivers.2005, 2, 123-130].According to the Nakagawa group, destruxins have shown to inhibit osteoclast bone resorption activity.Destruxin E reversibly induce morphological changes in osteoclast-like multinucleated cells (OCLs) at concentrations lower than those exhibiting the V-ATPase inhibitory activity [Bone, 2003, 33, 443].We investigated the total synthesis of destruxin E and its analogs, as well as their biological activity, to elucidate structure-activity relationships (SAR) for morphological changes in OCLs.