4-(1H-Pyrazol-1-yl) Benzenesulfonamide Derivatives: Identifying New Active Antileishmanial Structures for Use against a Neglected Disease

Molecules

Roberta K. F. Marra²  Alice M. R. Bernardino²  Tathiane A. Proux¹  Karen S. Charret³  Marie-Luce F. Lira¹  Helena C. Castro¹  Alessandra M. T. Souza⁴  Cesar D. Oliveira²  Júlio C. Borges²  Carlos R. Rodrigues⁴  Marilene M. Canto-Cavalheiro³  Leonor L. Leon³ 

[1] Programa de Pós-graduação em Ciências e Biotecnologia PPBI, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Baptista, Niterói, RJ, 24020-150, Brazil;Programa de Pós-graduação em Química, Instituto de Química, Universidade Federal Fluminense, Outeiro de São João Baptista, Niterói, RJ, 24020-150, Brazil;Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, RJ, 21040-900, Brazil;Faculdade de Farmácia, ModMolQSAR, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-590, Brazil;

关键词: pyrazoles;    benzenesulfonamide;    Leishmania;    cytotoxicity;    in silico evaluation;   

DOI  :  10.3390/molecules171112961

来源: mdpi

【 摘 要 】

Leishmaniasis is a neglected disease responsible for about 56,000 deaths every year. Despite its importance, there are no effective, safe and proper treatments for leishmaniasis due to strain resistance and/or drug side-effects. In this work we report the synthesis, molecular modeling, cytotoxicity and the antileishmanial profile of a series of 4-(1H-pyrazol-1-yl)benzenesulfonamides. Our experimental data showed an active profile for some compounds against Leishmania infantum and Leishmania amazonensis. The profile of two compounds against L. infantum was similar to that of pentamidine, but with lower cytotoxicity. Molecular modeling evaluation indicated that changes in electronic regions, orientation as well as lipophilicity of the derivatives were areas to improve the interaction with the parasitic target. Overall the compounds represent feasible prototypes for designing new molecules against L. infantum and L. amazonensis.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.