Biological properties of a benzothiazole-based mononuclear platinum(II) complex as a potential anticancer agent

Abstract

A mononuclear platinum(II) complex, [PtLCl]Cl (1, where L = N-(4-(benzo[d]thiazol-2-yl)phenyl)-2-(bis(pyridine-2-ylmethyl)-amino)acetamide), was synthesized by covalently tethering a benzothiazole derivative 2-(4-aminophenyl)benzothiazole to the 2,2′-dipicolylamine (DPA) chelating Pt^II center by an amidic bond. 1 showed a cytotoxicity comparable to that of cisplatin against MCF-7 cell lines and more potent activities against HeLa and A-549 cell lines. Investigation of the reaction of 1 with 5′-GMP displayed 1 could coordinate with N7-GMP to form the Pt-GMP adduct. Thus 1 has potential to form Pt-DNA adducts in vivo. Similarly, the glutathione (GSH) ligand could also coordinate to the Pt^II center to form a monodentate Pt-GS complex. The competition experiments of 1 with 5′-GMP and GSH showed that the coordination binding of 1 with GSH did not prevent formation of a certain amount of the Pt-GMP adduct in the reaction process. DNA binding experiments displayed that 1 could bind to DNA through multiple binding modes involving non-covalent interaction and monofunctional platination of the platinum(II) moiety, and induce a visible conformational change of DNA. The evaluation of the protein binding ability showed that 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.

Keywords:

• Mononuclear platinum(II) complex
• benzothiazole derivative
• cytotoxicity
• DNA binding
• human serum albumin

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We are grateful for financial supports from the National Natural Science Foundation of Hubei Province (No. 2018CFB658) and the Opening Project of Key Laboratory of Optoelectronic Chemical Materials and Devices, Ministry of Education, Jianghan University (No. JDGD-201810).