Novel anti-cancer agents based on germacrone: design, synthesis, biological activity, docking studies and MD simulations

Germacrone is a major activity component found in Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria. In the present study, novel germacrone derivatives were first designed based on the theories of bioalkylating agents, synthesized, and then investigated for their inhibition effects on Bel7402, HepG2, A549, and HeLa cells. Moreover, the study also evaluated the inhibition of these derivatives on c-Met kinase, which is expressed in a number of cancers. The results indicated that most of the compounds showed a stronger inhibitory effect on cancer cells and c-Met kinase than germacrone. Besides these findings, molecular docking studies were also carried out to analyze the results and explain the molecular mechanism of activities to c-Met kinase. Molecular dynamics simulations have been carried out for the further evaluation of binding stabilities between the compounds and their receptors.