DNA interaction of dioxycyclobutenedione-(1,2-cyclohexanediamine) platinum(II) complex with potential anticancer activity.
Dioxycyclobutenedione-(1,2-cyclohexanediamine)platinum(II), (R,R-DC-Pt) was found to have stronger cytotoxicity against six cancer cell lines than cisplatin and its DNA interactions was studied by calorimetric measurements, (13)C NMR. The binding specificity study of DNA base with R,R-DC-Pt was conducted by HPLC. To understand the molecular mechanism of R,R-DC-Pt with stronger cytotoxicity than that of cisplatin, we studied R,R-DC-Pt interaction with an oligonucleotide, d(ACCACGTGGT)(2), which contained c-H-ras gene encoding GGT by NMR spectroscopy. The oligomer DNA double helix was destroyed almost completely upon the R,R-DC-Pt binding. However under the same condition, the cisplatin binding with DNA was not so affected, and instead another conformation was formed, which suggests that larger damage to DNA can be induced by R,R-DC-Pt complex than that by cisplatin.
Yang
Ming
M
National Research Laboratory of Natural and Biomimatic Drugs, Peking University Health Science Center, PO Box 261, Beijing 100083, China. yangm@bjmu.edu.cn
Pang
Ruifang
R
Jia
Xin
X
Li
Qin
Q
Wang
Kui
K
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000187:drug effects*; D018736:DNA Adducts / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; D009944:Organoplatinum Compounds; D004247:DNA