Synthesis and biological activity of binuclear platinum complexes containing two monofunctional cis-[Pt(NH3)2Cl]+ units bridged by 4,4'-dipyridyl selenides or sulfides.
The synthesis of four binuclear platinum complexes of general formula ¿cis-[Pt(NH3)2Cl]2(L)¿ (NO3)2 [L is 4,4'-dipyridyl sulfide (compound I), 4,4'-dipyridyl selenide (compound II), bis(3-methyl-4-pyridyl) sulfide (compound III) or bis(3-methyl-4-pyridyl) selenide (compound IV)] has been achieved. These compounds have been characterized by elemental analysis, IR, 1H-NMR, 13C-NMR and 195Pt-NMR spectroscopy. The above dinuclear platinum complexes have been assayed for antitumor activity in vitro against the cisplatin-sensitive L1210 (the mice leukemia) and cisplatin-insensitive HCT8 (the human coloadenocarcinoma) cell lines. The compounds show IC50 values comparable to or higher than cisplatin against L1210 cell line; however, they have lower IC50 values than cisplatin against the cisplatin-insensitive HCT8 cell line. The complexes containing S exhibit a cytotoxicity against the two cancer cell lines superior to the Se analogues. DNA binding studies indicate the compound I possibly interacts with DNA nonintercalatively. The mode of DNA binding of the dinuclear Pt(II) complexes bridged by 4,4'-dipyridyl selenides or sulfides may be different to that of the aliphatic diaminebridged dinuclear Pt(II) complexes reported previously.
Zhao
G
G
Department of Chemistry, Nankai University, Tianjin, P.R. China.
Lin
H
H
Zhu
S
S
Sun
H
H
Chen
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D004247:DNA