Novel oxaliplatin derivatives with 1-(substituted benzyl)azetidine-3,3-dicarboxylate anions. Synthesis, cytotoxicity, and interaction with DNA.
A series of oxaliplatin derivatives with (1R,2R)-N(1) -alkyl-1,2-cyclohexane-1,2-diamine (alkyl=Bu or (i) Pr) as carrier ligands and 1-(methoxy- or methyl-substituted benzyl)azetidine-3,3-dicarboxylate anions as leaving groups were synthesized and spectrally characterized. Generally, Complexes 10-15 with an (i) Pr substituent at N(1) showed higher activities in vitro than carboplatin against MCF-7 human breast carcinoma and A549 human non-small-cell lung cell lines, although they were less potent than oxaliplatin. The typical complex 14 exhibited cytotoxicity superior to that of carboplatin and comparable to that of oxaliplatin against two selected tumor cell lines. Additionally, agarose gel electrophoresis was applied to investigate the DNA-cleavage ability of complex 14, which demonstrated that it has a different mode of DNA distortion from that of oxaliplatin.
Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, P. R. China (phone/fax: +86-25-83272381); Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Southeast University, Nanjing 211189, P. R. China.
Yanyan
Y
Sun
Zhe
Z
Cao
Shaohua
S
Gou
Tingting
T
Hu
D000838:Anions / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry* / Q000187:drug effects*; D003998:Dicarboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D000077150:Oxaliplatin; D010957:Plasmids; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000838:Anions; D000970:Antineoplastic Agents; D003998:Dicarboxylic Acids; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D004247:DNA
Antitumor activity; Cytotoxic activity; DNA; Oxaliplatin derivatives; Platinum complexes