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.

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

“…A series of 4-(1 H -pyrazol-1-yl)-benzenesulfonamides were synthesized and evaluated in vitro for their anti-leishmanial profile against Leishmania infantum and Leishmania amazonensis . Interestingly, 472 showed the best in vitro active profile against the infective L. amazonensis promastigotes and L. infantum forms, with IC 50 values of 0.059 and 0.070 mM, respectively [ 369 ]. Bekhit et al prepared a novel series of 1 H -pyrazole derivatives and tested for their in vitro anti-leishmanial activities against L. aethiopica promastigotes.…”

Pharmaceutical and medicinal significance of sulfur (SVI)-Containing motifs for drug discovery: A critical review

“…27) showed most potent activity against the tested L. infantum and L. amazonensis strains. In this case, both compounds 230 and 231 pyrazole baring sulfonamide groups were active for treating infections caused by these two Leishmania strains [164]. Borges and co-workers reported a new class of pyrazolyl benzenesulfonamide hybrids as potent antileishmanially active candidates against Leishmania amazonensis.…”

Screening of some pyrazole derivatives as promising antileishmanial agent

“…Chemotherapy for leishmaniasis is generally ineffective mainly due to the emergence of drug-resistant strains and toxicity of the therapeutic agents (Marra et al, 2012) The pentavalent antimonials compounds, such as sodium stibogluconate (pentostan) and meglumine antimoniate (glucantime) are widely used as primary therapy, but they induce toxic side effects together with drug resistance (dos et al, 2011;Braga et al, 2007).…”

“…The epidemiological pattern of Leishmania species is changing, with a tendency to urbanization and geographic expansion. Despite the high worldwide prevalence, no vaccine for Leishmaniasis and complex vector control, few advances were made in the treatment of this disease ((dos et al, 2011;Marra et al, 2012).…”