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

• Published in: Journal of molecular structure 2023-08, Vol.1285, p.135405, Article 135405
• Main Authors: Gudimani, Parashuram, Hebbar, Nagashree U, Shastri, Samundeeswari L, Shastri, Lokesh A., Shettar, Arun K, Hoskeri, Joy H, Joshi, Shrinivas, Sunagar, Vinay A
• Format: Article
• Language: English
• Subjects: Anti-inflammatory; Antimicrobial; Lonazolac; Pyrazole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135405

•Efficient synthetic route for the synthesis oftri-substituted propanoic acid derivatives which are analogous to known drug lonazolac.•Synthesized scaffolds were assessed for their in-vitro anti-inflammatory activity against MMP-2 and MMP-9using micro-broth dilution assay.•The scaffolds were proven to be having 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.•The scaffolds may be considered for in-vivo use as lead drug. 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. [Display omitted]