Comparison of the mode of action of a dinuclear platinum complex containing a pyridine derivative with its monomeric analog.
The DNA binding and interstrand cross-linking properties of the dinuclear platinum complex [¿cis-Pt(NH3)2Cl¿2bpsu](NO3)2 (bpsu is 4,4'-dipyridyl sulfide) (II) and the mononuclear complex [cis-Pt(NH3)2Cl(4-methylpyridine)]NO3 (I) were compared with those of [¿cis-Pt(NH3)2Cl¿2H2N(CH2)4NH2](NO3)2 (III) in order to understand the mode of action of complexes I and II. Both compound I and compound II caused significantly different changes of conformation in poly(dG-dC) x poly(dG-dC) than compound III did. Studies of DNA binding, interstrand cross-linking and fluorescence assay suggest that compound I monofunctionally binds to DNA and compound II bifunctionally binds to DNA, that the dinuclear platinum complex II more efficiently interacts with DNA compared to its monomeric analog, and that platinum I and II complexes both interact with DNA in a non-intercalative mode. All the results indicate that the mode of action of the dinuclear complex II is different from that of the mononuclear complex I.
Zhao
G
G
Department of Chemistry, Nankai University, Tianjin, PR China.
Lin
H
H
Yu
P
P
Sun
H
H
Zhu
S
S
Chen
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013950:Thymus Gland / Q000737:chemistry
C116611:((cis-Pt(NH3)2Cl)2 bpsu(NO3)2); C116613:(Pt(NH3)2Cl(4-methylpyridine))NO3; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011725:Pyridines; D004247:DNA