CIS-BIS(PYRIDINE)PLATINUM(II) ORGANOAMIDES WITH UNEXPECTED GROWTH-INHIBITION PROPERTIES AND ANTITUMOR-ACTIVITY

被引：41

作者：

WEBSTER, LK ^{[1
]}

DEACON, GB ^{[1
]}

BUXTON, DP ^{[1
]}

HILLCOAT, BL ^{[1
]}

JAMES, AM ^{[1
]}

ROOS, IAG ^{[1
]}

THOMSON, RJ ^{[1
]}

WAKELIN, LPG ^{[1
]}

WILLIAMS, TL ^{[1
]}

机构：

[1] MONASH UNIV,DEPT CHEM,CLAYTON,VIC 3168,AUSTRALIA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 18期

关键词：

D O I：

10.1021/jm00096a007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The platinum(II) organoamides [Pt(NRCH2)2L2] (L = pyridine (py), R = p-HC6F4, C6F5, p-IC6F4, p-ClC6F4, p-C6F5C6F4; L-4-methylpyridine, R = p-HC6F4) and [Pt(NRCH2CH2NR')(py)2] (R = p-HC6F4, R' = C6F5, p-BrC6F4, or p-MeC6F4) inhibit the growth of murine L1210 leukemia cells in culture with ID50 values for continuous exposure in the range 0.6-2.7-mu-M. Representative complexes are also active against L1210 cells in 2-h pulse exposures, as well as against the cisplatin-resistant variant L1210/DDP and human colonic carcinoma cell lines HT 29 and BE. Three complexes [Pt(NRCH2)2L2] (R = p-HC6F4, C6F5, or p-IC6F4) have good activity (T/C greater-than-or-equal-to 180%) against P388 leukemia in mice, and all other compounds tested are active except when R = p-C6F5C6F4, L = py. Although the molecular basis of the biological activity of these complexes is not known, the observation of good activity for amineplatinum(II) compound with no hydrogen substitutents on the nitrogen donor atoms introduces a new factor in the anticancer behavior of platinum(II) complexes.

引用

页码：3349 / 3353

页数：5

共 23 条

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