Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A critical role played by the conjugated trienyl lactone moiety.

Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, two new analogs, ZJ-105 and ZJ-106, were designed and synthesized to probe the importance of the conjugated trienyl lactone moiety of the molecule by replacing the C2-C3 double bond in ZJ-101 with a single bond and switching the geometry of the C4-C5 double bond in ZJ-101 from Z to E, respectively. Biological evaluation showed that ZJ-105 completely loses antiproliferative activity whereas ZJ-106 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the conjugated trienyl lactone moiety of the molecule is critical for its anticancer activity.

Insights into the structure-activity relationship of the anticancer compound ZJ-101: A critical role played by the cyclohexene ring.

Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, a new analog ZJ-102 was designed and synthesized to probe the importance of the cyclohexenyl group through its replacement to a phenyl group using a concise and convergent synthetic approach. The biological evaluation showed that this new analog ZJ-102 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the cyclohexenyl ring (along with its two stereogenic centers) present in ZJ-101 is important for its anticancer activity.