Synthesis and Cytotoxic Evaluation of Eremophilane Sesquiterpene 07H239-A Derivatives

Nine new derivatives (6—14) of the eremophilane sesquiterpene 07H239-A (5) were designed and semisynthesized with two types of R-groups by amidation. Most of them were active against five human tumor cell lines, and compounds 6—10 were more potent than the natural product 5. In particular, compounds 6 and 9 exhibited the strongest cytotoxic activity against MDA-MB-435 with IC50 values of 0.91 and 0.96 μM, respectively. Preliminary structure–activity relationships (SARs) analysis indicated that the 14-carboxyl in 5 was an ideal target for chemical modification, and the side chain of 5 might play a necessary role in facilitating their cytotoxic potencies.