Pt(II) pyridinium amidate (PYA) complexes: Preparation and in vitro anticancer activity studies

Abstract

N-[1-Alkylpyridin-4(1H)-ylidene]amides (PYAs), also known as pyridinium amidates, are a class of recently introduced ligands for transition metal ions. Herein we report the synthesis of the Pt(PYA) complexes [PtCl(DMSO)(HL)]Cl2 (1), [Pt(CH3)(DMSO)(L)]Cl (2) and [Pt(CH3)(PPh3)(L)]Cl (3) (L = N-(1-benzylpyridin-4(1H)-ylidene)picolinamide). L and [HL]+ act as bidentate ligands coordinating through the pendant pyridine and either the amidate oxygen or nitrogen atoms to give the corresponding N,O or N,N linkage isomers. DFT calculations were carried out to determine the most energetically favorable isomeric forms of these compounds. For 1 the N,O coordination mode was lower in energy, while for 2 and 3 hardly any difference was found. In vitro cytotoxicity studies of [HL]Cl and 1 in human colorectal carcinoma HCT116, non-small cell lung carcinoma NCI-H460, and cervical carcinoma SiHa cells showed that both compounds are cytotoxic in the low lM range.