Affordable Access

Publisher Website

Second generation of 5-ethenylbenzofuroxan derivatives as inhibitors ofTrypanosoma cruzigrowth: Synthesis, biological evaluation, and structure–activity relationships

Authors
Journal
Bioorganic & Medicinal Chemistry
0968-0896
Publisher
Elsevier
Publication Date
Volume
15
Issue
7
Identifiers
DOI: 10.1016/j.bmc.2007.01.009
Keywords
  • Ethenylbenzofuroxans
  • Wittig Reaction
  • T. Cruzi
Disciplines
  • Biology
  • Design

Abstract

Abstract In vitro growth inhibitory activity of 21 new 5-ethenylbenzofuroxan derivatives against the protozoan parasite Trypanosoma cruzi, the causative agent of American trypanosomiasis, was studied. The designed compounds possess the previously described exigencies for optimal anti-parasite activity, the 5-ethenylbenzofuroxanyl moiety with different substituents. The synthetic key for preparing the derivatives was the Wittig procedure, that when 5-formylbenzofuroxan was used as the electrophile the corresponding deoxygenated products were marginally generated. Four of the new derivatives displayed remarkable in vitro activities against the epimastigote form of three strains of T. cruzi, Tulahuen 2, CL Brener, and Y. While the three deoxygenated analogues biologically assayed resulted inactives. Unspecific cytotoxicity was evaluated using human macrophages and active derivatives were not toxic at a concentration at least 13 times that of its IC 50 against T. cruzi (CL Brener strain). From the preliminary structure–activity relationship studies lipophilicity and electronic requirements were found relevant to anti- T. cruzi activity. Active compounds are more lipophilic than inactive ones and it was also identified that an optimum value of R Swain-Lupton’s descriptor is required for optimal activity.

There are no comments yet on this publication. Be the first to share your thoughts.