Synthesis and in vitro biological activities of ferrocenyl-chalcone amides

A series of aminoferrocenyl-chalcone amides 11-19 were synthesized through condensation of a carboxylic acid-functionalized chalcone 10 with ferrocenylamines, using 1,1'-carbonyldiimidazole as the coupling agent. The compounds were screened for their antiplasmodial activities against CQS 3D7 and CQR FCR3 strains of Plasmodium falciparum. All compounds were found to be active, with IC50 values ranging between 0.5-4.5 and 2.1-6.6 A mu M against 3D7 and FCR3, respectively. Amide 11, featuring a 2-aminoethylene linker, was the most active of all, with IC50 values of 2.6 and 2.1 A mu M against the 3D7 and FCR3 strains, respectively. In screens against a panel of three cancer cell lines, i.e., TK-10, UACC-62, and MCF-7, amide 19, with a piperazinyl linker, showed increased activity against all three cell lines, compared to the reference drug, parthenolide. Antimicrobial assays that had been performed on six different microorganisms revealed that most of the synthesized amides were inactive against all of these microorganisms. Compound 17, however, with an aminodi(ethyleneoxy) linker, displayed moderate bactericidal activity against the gram-negative microorganisms, with a MIC100 value of 128 A mu M. The outcomes of this study may hence significantly contribute toward malaria and cancer chemotherapy research, and more generally to the growing body of research that aims at illustrating the potential of employing organometallic compounds in medicinal chemistry programs.