Synthesis, characterization and antitumor activity of new type binuclear platinum(II) complexes.
Five new type binuclear platinum(II) complexes (a-e) have been synthesized and characterized by elemental analysis, conductivity, thermal analysis, IR, UV, (1)H NMR and mass spectral techniques. The cytotoxicity of the complexes was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The acute toxicity and antitumor activity of complex ein vivo were also studied. The results indicate that complexes a-d have no activity against HL-60, MCF-7, BGC-823, EJ and HCT-8 cell lines, with a higher IC(50) value (>50 microM). Complex e confers substantially greater cytotoxicity against HL-60, MCF-7, BGC-823, EJ and HCT-8 cell lines with an IC(50) value of 0.02+/-0.009, 1.70+/-0.21, 4.00+/-0.35, 0.98+/-0.02 and 1.02+/-0.21 microM, respectively. LD(50) of complex e is 815.3mg/kg, it was significantly higher than that of cisplatin and carboplatin. Complex e at dose of 4, 12 and 20mg/kg has no activity against mouse hepatocarcinoma H22 and Lewis lung carcinoma in mice, but displays significant activity against human ovarian carcinoma A2780 and human colon carcinoma HCT-116 in nude mice at dose of 12 mg/kg, and activity is similar to that of cisplatin at dose of 4 mg/kg. Complex e at dose of 20mg/kg has no activity against human lung adenocarcinoma A549 in nude mice (P>0.05). The results suggest that the species of amine for the new type binuclear platinum complexes have important effect on their cytotoxicity, and they may be a new class platinum anticancer drugs.
College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
Jinchao
J
Zhang
Lei
L
Liu
Yuqiu
Y
Gong
Xiaoming
X
Zheng
Mengsu
M
Yang
Jingrong
J
Cui
Shigang
S
Shen
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds