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2007-12-01 - Article/Dans un journal avec peer-review - Anglais - 7 page(s)

Huang T.L., Bacchi C.J., Kode N.R., Zhang Q., Wang G., Yartlet N., Rattendi D., Londono I., Mazumder L., Vanden Eynde Jean-Jacques , Mayence A., Donkor I.O., "Trypanocidal Activity of Piperazine-linked Bisbenzamidines and Bisbenzamidoximes, an Orally Active Prodrug" in International Journal of Antimicrobial Agents, 30, 6, 555 – 561

  • Edition : Elsevier Science, Amsterdam (The Netherlands)
  • Codes CREF : Chimie organique (DI1313)
  • Unités de recherche UMONS : Chimie organique (S836)
Texte intégral :

Abstract(s) :

(Anglais) 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% (IC(50))=1.7-3.0 nM) or cyclic octyl group (17, IC(50)=2.3-4.6 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.

Identifiants :
  • PMID : 17920820
  • DOI : 10.1016/j.ijantimicag.2007.07.021