Enhanced anti-cancer efficacy to cancer cells by a novel monofunctional mononuclear platinum(ii) complex containing a mixed S, N, S-donor ligand. (21st June 2017)

• Record Type: Journal Article
• Authors: Chen, Zhanfen; Zhang, Shuping; Zhang, Jian; Zhu, Zhenzhu
• Is Part Of: New journal of chemistry. Volume 41:Number 14(2017)
• Page Start: 6760
• Page End: 6768
• Publication Date: 2017-06-21
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c7nj01472d
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : A novel platinum–intercalator hybrid complex (1 ) exhibits a cytotoxicity comparable to that of cisplatin against MCF-7 cell lines, and more potent activities against HeLa and A-549 cell lines, especially against the former. Abstract : A novel mononuclear platinum(ii ) complex, [PtL Cl]Cl (1, whereL = N -(4-(benzo[ d ]oxazol-2-yl)phenyl)-2-(bis(2-ethylthioethyl)amino)acetamide), was synthesized containing an S, N, S -donor monochloroplatinum(ii ) moiety tethered to a planar 2-(4-aminophenyl)benzoxazole unit by an amidic bond. [PtL′ Cl]Cl (2, whereL′ = bis(2-ethylthioethyl)amine), the tridentate chelating Pt II motif of1, was also synthesized. Complex1 exhibited a cytotoxicity comparable to that of cisplatin against MCF-7 cell lines and slightly higher activities against HeLa and A-549 cell lines. Compared to the activities of2, L, andL′, the potent cytotoxicity of1 should result from two aspects: the platinum moiety and the 2-(4-aminophenyl)benzoxazole unit. DNA binding experiments demonstrated that1 could bind to DNA in a dual binding mode, i.e., intercalation plus monofunctional platination, and 2-(4-aminophenyl)benzoxazole unit in1 's structure should act as an intercalating group. Investigations of the reaction of1 with 5′-GMP showed that1 could coordinate with N7-GMP to form the Pt–GMP adduct. Thus, 1 has the potential to form monofunctional Pt–DNA adducts in vivo . Similarly, the glutathione (GSH) ligand could also be coordinated to the Pt(ii ) center to form a monodentate Pt–GS complex. However, the reaction towards GSH was indeed retarded by the bulky ligand of1, implying that the side-effects related to GSH might be reduced in vivo . The competition experiments of1 with 5′-GMP and GSH showed that1 reacted much faster with GSH than with 5′-GMP, but this did not prevent the formation of a certain amount of the Pt–GMP adduct.