Leishmania amazonensis Growth Inhibitors: Biological and Theoretical Features of Sulfonamide 4-Methoxychalcone Derivatives |
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Authors: | Alessandra M T Souza Helena C Castro Monique A Brito Carla R Andrighetti-Fröhner Uiaran Magalhães Kely N Oliveira Daniela Gaspar-Silva Letícia K Pacheco Antônio C Joussef Mário Steindel Cláudia M O Simões Dilvani O Santos Magaly G Albuquerque Carlos R Rodrigues Ricardo J Nunes |
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Institution: | 1. ModMolQSAR, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, CEP 21941-590, Brazil 2. LABioMol, GCM, Instituto de Biologia and Faculdade de Farmácia, Universidade Federal Fluminense (UFF), Niterói, RJ, CEP 24001-970, Brazil 3. Faculdade de Farmácia, Universidade Federal Fluminense (UFF), Niterói, RJ, CEP 24001-970, Brazil 4. Departamento de Química, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, SC, Brazil 5. Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, SC, Brazil 6. Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, SC, Brazil 7. Departamento de Química Organica, Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Ilha do Fund?o, Cidade Universitária, Rio de Janeiro, RJ, 21941-909, Brazil
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Abstract: | Current drugs for treating leishmaniasis are still associated with significant toxicity and failure rates. Thus, new effective and less toxic antileishmanial agents are still in need. Herein, we tested a series of sulfonamide 4-methoxychalcone derivatives against L. amazonensis promastigote and amastigote forms to identify its antileishmanial profile against this species compared to L. braziliensis. In addition, we used molecular modeling tools to determine stereoelectronic features that may lead to the antileishmanial profile. Interestingly, all tested compounds were able to affect L. amazonensis promastigote form in a concentration-dependent manner and with low cytotoxicity, except for derivative 3g. However, our results showed that compound 3f (para-Cl) presents the best profile against both L. amazonensis forms (promastigote and amastigote), differently from that observed for L. braziliensis, when compound 3i was the most active. Structure–activity relationship (SAR) analysis of these derivatives pointed molecular volume, HOMO density, and conformational aspects as important characteristics for parasitic profile. Overall, sulfonamide 4-methoxychalcone derivatives may be pointed out not only as lead compounds for treating leishmaniasis (i.e., 3f) but also as experimental tools presenting parasite-selectivity (i.e., 3i). |
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