title: 4-(1H-Pyrazol-1-yl) benzenesulfonamide derivatives: identifying new active antileishmanial structures for use against a neglected disease.
abstract: 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.
authors.affiliation: Programa de Pós-graduação em Química, Instituto de Química, Universidade Federal Fluminense, Outeiro de São João Baptista, Niterói, RJ, Brazil. katlenfusco@bol.com.br
authors.forename: Roberta K F
authors.initials: RK
authors.lastname: Marra
authors.forename: Alice M R
authors.initials: AM
authors.lastname: Bernardino
authors.forename: Tathiane A
authors.initials: TA
authors.lastname: Proux
authors.forename: Karen S
authors.initials: KS
authors.lastname: Charret
authors.forename: Marie-Luce F
authors.initials: ML
authors.lastname: Lira
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.forename: Alessandra M T
authors.initials: AM
authors.lastname: Souza
authors.forename: Cesar D
authors.initials: CD
authors.lastname: Oliveira
authors.forename: Júlio C
authors.initials: JC
authors.lastname: Borges
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Marilene M
authors.initials: MM
authors.lastname: Canto-Cavalheiro
authors.forename: Leonor L
authors.initials: LL
authors.lastname: Leon
authors.forename: Veronica F
authors.initials: VF
authors.lastname: Amaral
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects*; D007894:Leishmania mexicana / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008968:Molecular Conformation; D010419:Pentamidine / Q000494:pharmacology; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D013449:Sulfonamides; D014344:Trypanocidal Agents; D010419:Pentamidine