Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent antitrypanosomal activity

被引:56
作者
Bi, Xiangdong
Lopez, Christina
Bacchi, Cyrus J.
Rattendi, Donna
Woster, Patrick M.
机构
[1] Wayne State Univ, Dept Pharmaceut Sci, Detroit, MI 48202 USA
[2] Pace Univ, Haskins Labs, New York, NY 10038 USA
[3] Pace Univ, Dept Biol & Hlth Sci, New York, NY 10038 USA
关键词
polyamine; trypanothione; trypanothione reductase; trypanosome; trypanosomiasis; inhibitor; antiparasitic; guanidine; biguanide;
D O I
10.1016/j.bmcl.2006.03.048
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of polyaminoguanidines and polyaminobiguan ides were synthesized and evaluated as potential antitrypanosomal agents. These analogues inhibit trypanothione reductase (TR) with IC50 values as low as 0.95 mu M, but do not inhibit the closely related human enzyme glutathione reductase (GR). The most effective analogues, 7a, 7b and 8d, inhibited parasitic growth in vitro with IC50 values of 0.18, 0.09 and 0.18 mu M, respectively. These agents represent a promising new class of potential antitrypanosomal agents. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3229 / 3232
页数:4
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