Structure-based design to explore the anticancer efficacy of organometallic Pt(ii)- and Au(iii)-N-heterocyclic carbene (NHC) complexes

Abstract

Cancer is one of the leading public health concerns globally, and therefore better drugs are required for treatment. Several strategies have been taken to improve the success of drug discovery. Our strategy is the exploration of the organometallic complexes of the platinum group metals as potential anticancer drugs. Organometallic complexes bearing N-heterocyclic carbene (NHC) ligands are getting attention for therapeutic purposes. The synthesis, structure, and anticancer activities of platinum(II)- and gold(III)-N-heterocyclic carbene complexes supported by pro-ligand 1-methyl-2-(pyridylmethyl)imidazo[1,5-a]pyridin-4-ylium hexafluorophosphate, (1.HPF₆) are described. Two novel isoelectronic and isostructural complexes, viz. [Pt(1)Cl₂] (2) and [Au(1)Cl₂][AuCl₄] (3), have been synthesized and characterized using a series of spectroscopic techniques. Finally, the square planar geometry of 3 was established by single crystal X-ray diffraction studies. Interestingly, complex 3 possesses Cl–Cl interactions and this is the first organogold complex to bear the same. Molecular docking analysis revealed the highest free binding energy for complex 3 with human-DNA topoisomerase. Finally, in vitro anticancer studies on breast cancer cell line, MDA-MB231, revealed Au(III)–NHC complex 3 is more potent than Pt(II)–NHC complex 2.