Second generation of 5-ethenylbenzofuroxan derivatives as inhibitors of Trypanosoma cruzi growth: Synthesis, biological evaluation, and structure–activity relationships
| Autor: | Ana I. Gómez de Castro, Mercedes González, Gabriela Aguirre, Ana M. Ferreira, Lucía Boiani, Mariana Boiani, Alicia Merlino, Williams Porcal, Hugo Cerecetto, Rossanna Di Maio, Paola Hernández |
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| Rok vydání: | 2007 |
| Předmět: |
Chagas disease
Cell Survival Stereochemistry Trypanosoma cruzi Clinical Biochemistry Pharmaceutical Science Biochemistry Chemical synthesis Cell Line Structure-Activity Relationship parasitic diseases Drug Discovery medicine Animals Humans Moiety Cytotoxicity Molecular Biology IC50 Benzoxazoles biology Chemistry Macrophages Organic Chemistry biology.organism_classification medicine.disease Trypanocidal Agents In vitro Lipophilicity Molecular Medicine Indicators and Reagents |
| Zdroj: | Bioorganic & Medicinal Chemistry. 15:2768-2781 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2007.01.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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