Guanidine Derivatives Containing the Chalcone Skeleton Are Potent Antiproliferative Compounds against Human Leukemia Cells

Abstract

In this study, we investigated the effects of eleven synthetic guanidines containing the 1,3-diphenylpropenone core on the viabilities of six human cancer cells. The most cytotoxic compound against human cancer cells of this series contains a N-tosyl group and a N-methylpiperazine moiety 6f. It was cytotoxic against leukemia cells (U-937, HL-60, MOLT-3, and NALM-6) with significant effects against Bcl-2-overexpressing U-937/Bcl-2 cells as well as the human melanoma SK-MEL-1 cell line. It exhibited low cytotoxicity against quiescent or proliferating human peripheral blood mononuclear cells. The IC50 value for the leukemia U-937 cells was 1.6 ± 0.6 µM, a similar value to that in the antineoplastic agent etoposide. The guanidine containing a N-phenyl substituent 6i was also as cytotoxic as the guanidine containing the N-tosyl substituent and the N-methylpiperazine group 6f against human U-937 leukemia cells and both synthetic guanidines were potent apoptotic inducers. Cell death was mediated by the activation of the initiator caspase-9 and the executioner caspase-3, and associated with the release of cytochrome c. These synthetic guanidines are potent cytotoxic compounds against several human leukemia cells and even the human melanoma cell line SK-MEL-1 and might be useful in the development of new strategies in the fight against cancer.

Anticancer Potential of Natural Chalcones: In Vitro and In Vivo Evidence

“…In addition to these actions, chalcones have also attracted attention due to their ability to modulate the process of carcinogenesis at different levels [ 10 , 11 ]. Regarding anticancer effect, we and others have reported the growth-inhibitory effect of numerous chalcones in vitro [ 12 , 13 , 14 , 15 ] or the anticancer effect in vivo [ 16 , 17 ]. Additionally, multimodal pharmacological effects of chalcones on cellular and molecular levels have been recently reviewed [ 18 ].…”