DNA-binding property and antitumor activity of a cyclam bridged dinuclear platinum(II) complex

The design of multinuclear Pt(II) complexes with novel structural feature is very important in the search for new anticancer agents. In this work, a dinuclear platinum(II) complex [Pt2(DTBPA)Cl2] (II) [DTBPA = (2,2′-(4,11-dimethyl-1,4,8,11-tetraazacyclotetradecane-1,8-diyl)bis(N-(2-(pyridin-2-yl)ethyl)acetamide))] was synthesized via two different methods and characterized by NMR, IR, electrospray mass spectrometry and elemental analysis. It binds to calf thymus DNA (CT-DNA) and induces its conformational changes. Gel electrophoresis data show that complex II leads to a clear decrease of migration rate of the negatively supercoiled band (form I) of supercoiled pUC19 plasmid. The cytotoxic activity of the complex II was tested against human cervical cancer cell line (Hela) and human ovarian carcinoma cell line (Caov-3) and compared with cisplatin. It displays more potent cytotoxicity against Hela cell line than cisplatin at low concentration range.

A new cyclam bridged dinuclear platinum complex [Pt2(DTBPA)Cl2] (II) [DTBPA = (2,2′-(4,11-dimethyl-1,4,8,11-tetraazacyclotetradecane-1,8-diyl)bis(N-(2-(pyridin-2-yl)ethyl)acetamide))] was synthesized and fully characterized. This complex binds mildly to DNA. It shows high cytotoxicity against human Hela cell at concentrations below 10−6 M.Figure optionsDownload as PowerPoint slide