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

•Preparation of Pt anticancer agents with low μM cytotoxic activity.•Synthesis of organometallic and coordination compounds of Pt.•N-[1-alkylpyridin-4(1H)-ylidene]amides (PYAs) as ligand systems.•DFT calculations of the energetically favorable complex isomeric forms.

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 μM range.

Graphical abstractPt complexes of the bidentate ligands L and [HL]+ (L = N-(1-benzylpyridin-4(1H)-ylidene)picolinamide) were prepared. Coordination occurs through the pendant pyridine and either the amidate oxygen or nitrogen atoms. DFT calculations revealed the energetically most favorable coordination mode. Cytotoxicity in the low μM range was found for selected compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide