A new approach for the synthesis of tri-substituted pyrazole propionic acids derivatives: Anti-inflammatory, antimicrobial and molecular docking studies

Abstract

The present study involves design, synthesis and biological evaluation of novel 3-(3,5-diphenyl-1H-pyrazol-4-yl)-3-(aryl)propanoic acid 6(a-f) and propanoate 7(a-f) derivatives which are analogous to the known drug lonazolac. The pyrazole derivative of lonazolac exhibiting interesting biological activities, such as antimicrobial, antifungal and anti-inflammatory etc. Therefore, the targeted moieties were synthesised in their pure form without the use of column chromatography. All the synthesised moieties were examined against MMP-2 and MMP-9 anti-inflammatory activity in comparison with tetracycline. Compound 6(a-f) series showed more than 80% and 70% inhibition against MMP-2 and MMP-9 respectively. Wherein, 7(a-f) series showed moderate percentage of inhibition against both MMP-2 and MMP-9. The antimicrobial activity was performed by micro-broth dilution assay using Itraconazole and ciprofloxacin as reference. The targets have shown promising biological activities. Docking studies of the molecule on crystal structure of E. coli have shown good docking score with similar interactions as that of the standard clorobiocin.