Cyclometalated platinum(II) complexes as topoisomerase IIα poisons.
A platinum(II)-based major groove binder [Pt(II)(C^N)(C≡NR)(2)](+) (HC^N = 2-phenylpyridine (phpy), R = 2-naphthyl) was identified as a potent human topoisomerase IIα poison. It stabilizes the covalent TopoIIα-DNA cleavage complex and induces cancer cell death with potency significantly higher than the widely clinically used TopoIIα poison Vp-16.
Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong.
Jia
J
Liu
Chung-Hang
CH
Leung
Andy Lok-Fung
AL
Chow
Raymond Wai-Yin
RW
Sun
Siu-Cheong
SC
Yan
Chi-Ming
CM
Che
D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000633:toxicity; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry* / Q000633:toxicity; D010984:Platinum / Q000737:chemistry*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry* / Q000633:toxicity
D000951:Antigens, Neoplasm; D056831:Coordination Complexes; D004268:DNA-Binding Proteins; D007364:Intercalating Agents; D059005:Topoisomerase II Inhibitors; D010984:Platinum; D004250:DNA Topoisomerases, Type II