A novel platinum(ii) anticancer complex of danysl bis(2-benzothiazolylmethyl)amine with dimethyl sulfoxide as a leaving group: synthesis, cytotoxicity, interaction with DNA and human serum albumin

Abstract

A novel mononuclear platinum(II) complex, [PtL(DMSO)Cl]Cl (1, here L = danysl bis(2-benzothiazolylmethyl)amine), has been synthesized and characterized by ESI-MS, IR spectrum, ¹H NMR, ¹³C NMR, molar conductivity, and elemental analysis. The results suggest that in the structure of complex 1, a platinum(II) ion is coordinated by a tertiary amine nitrogen, a benzothiazole nitrogen, a DMSO sulfur, and an exogenous chlorine ion to form one square mononuclear structure. Complex 1 exhibits a cytotoxicity comparable to that of cisplatin against HeLa cell line and more potent activities against A-549 and MCF-7 cell lines. Compared to those of L, the potent cytotoxicity of 1 should result from the coordination of Pt(II). DNA binding experiments demonstrate that 1 could strongly bind to calf thymus DNA (CT-DNA) by a groove binding mode accompanied with a moderate intercalation and induce a visible conformational variation of DNA. Investigation of the reaction of 1 with 5′-GMP by ESI-MS shows that complex 1 could first form a 1 : 1 adduct [PtL(DMSO)(GMP) − 2Na + H]⁺ with 5′-GMP and react further with a second equivalent of 5′-GMP to form a 1 : 2 adduct [PtL(DMSO)(GMP)₂ − 4Na + 3H]⁺, which is similar to those of [Pt(en)(DMSO)Cl]Cl and cisplatin. Therefore, the anticancer mechanism of these compounds might well be related to each other. The evalution of the protein binding ability shows that complex 1 could bind to human serum albumin (HSA) with a moderate binding affinity, quench the intrinsic fluorescence of HSA, and destroy the tertiary structure of HSA.