Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3360753 | International Journal of Antimicrobial Agents | 2007 | 7 Pages |
Abstract
A series of 32 piperazine-linked bisbenzamidines (and related analogues) were analysed for their in vitro and in vivo trypanocidal activity against a drug-sensitive strain of Trypanosoma brucei brucei and a drug-resistant strain of Trypanosoma brucei rhodesiense. The compounds showed similar potencies against both strains. The most potent compounds were bisbenzamidines substituted at the amidinium nitrogens with a linear pentyl group (8, inhibitory concentration for 50% (IC50)Â =Â 1.7-3.0Â nM) or cyclic octyl group (17, IC50Â =Â 2.3-4.6Â nM). Replacement of the diamidine groups with diamidoxime groups resulted in a prodrug (22) that was effective orally against T. b. brucei-infected mice. Three compounds (7, 11 and 15) provided 100% cure when administered parenterally. The results indicate that the nature of the substituents at the amidinium nitrogens of bisbenzamidines strongly influence their trypanocidal activity.
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Authors
Tien L. Huang, Cyrus J. Bacchi, Nageswara R. Kode, Qiang Zhang, Guangdi Wang, Nigel Yartlet, Donna Rattendi, Indira Londono, Lakshman Mazumder, Jean Jacques Vanden Eynde, Annie Mayence, Isaac O. Donkor,