The interactions of (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) and related compounds with deoxyribonucleic acid.
The interactions of a new antitumor platinum (Pt) complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114R, 2) and its related compounds, cis-diamminedichloroplatinum(II) (CDDP, 1), trans-diamminedichloroplatinum(II) (TDDP, 3), (+)-(S)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114S, 4), (R)-2-aminomethylpyrrolidinedichloroplatinum(II) (5) and cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA, 6), with calf-thymus deoxyribonucleic acid (DNA) and DNA nucleosides were investigated by ultraviolet (UV) and circular dichroism (CD) spectrometry. The UV spectra of the DNAs treated with these Pt complexes exhibited both bathochromic shift and hyperchromicity, showing a binding of Pt to the heterocyclic groups of these DNA as well as an alteration in the secondary structure of DNA. The reaction rates of the Pt complexes with DNA, however, differed from one another, and the order was CDDP, TDDP, 5 much greater than DWA2114R, S greater than CBDCA. The CD spectra of the DNAs treated with the Pt complexes, except TDDP, at a low Pt ratio (less than approximately (ca.) 0.1 of Pt bound to DNA/DNA base molar ratio) exhibited an increase of ellipticity at ca. 275 nm. The melting temperature of the DNAs treated with DWA2114R or CDDP were almost the same as the native DNA, while the melting temperature with TDDP was higher by 7-8 degrees C than that of the native DNA. All the Pt complexes reacted with 2'-deoxyguanosine (dG), 2'-deoxyadenosine and 2'-deoxycytidine, but none reacted with thymidine. The CD spectral change of the dG was largest. DWA2114R reacted faster with dG than other nucleosides.
Morikawa
K
K
Exploratory Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba-shi, Japan.
Matsumoto
T
T
Matsuoka
Y
Y
Koizumi
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D004247:DNA / Q000187:drug effects*
D000970:Antineoplastic Agents; C058816:DWA 2114; D004247:DNA; D016190:Carboplatin