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.