Synthesis, molecular modeling and biological screening of some pyrazole derivatives as antileishmanial agents.

Abstract

Novel open chain and cyclized derivatives containing pyrazole scaffold were designed, synthesized and evaluated as antileishmanial compounds. Methodology &results: In silico reverse docking experiment suggested Leishmania major pteridine reductase (Lm-PTR1) as a putative target for the synthesized compounds. In vitro antileishmanial screening against L. major promastigotes and amastigotes using miltefosine and amphotericin B as references showed that the majority of the compounds displayed activity higher than miltefosine. Compounds 3i and 5 showed the highest antileishmanial activity with IC50 values of 1.45±0.08μM and 2.30±0.09μM, respectively, for the amastigote form. In silico drug-likeness and toxicity predictions showed acceptable profiles for most of the compounds, which were validated by experimental toxicity studies. This study offers promising entities for antileishmanial activity.