4-Aminoantipyrine Analogs as Anti-inflammatory and Antioxidant agents: Synthesis, Biological Evaluation and Molecular Docking Studies

Abstract

Objectives: A novel series of 4-aminoantipyrine derivatives were designed and efficiently synthesized from Gewald, triphosgene and various substituted aromatic/ aliphatic/heterocyclic amines. Methods: The synthesized derivatives were characterized by IR, NMR, Mass and elemental analysis. The synthesized derivatives were evaluated for their anti-inflammatory activity using in vitro protein denaturation assay and antioxidant activity by using the 1,1-diphenyl-1-picrylhydrazyl free radical scavenging method. To establish the selectivity and safety profile of the drug, the most active compounds 4a and 4b were further screened for cytotoxicity against HeLa and MCF-7 cell lines using the sulforhodamine-B assay. The synthesized compounds were also analyzed for ADME properties and a docking study was done into the active site of oxidoreductase, cyclooxygenase-1 and cyclooxygenase-2 enzymes in an attempt to understand their binding mode using Auto Dock Vina. Results: Among the series Compounds 4a and 4b showed potent anti-inflammatory activity and antioxidant activity as compared with standard diclofenac and Ascorbic acid respectively. The results of in silico ADME Screening showed that compounds could be exploited as an oral drug candidate. The most prominent compound 4a and 4b showed no significant cytotoxic activity against HeLa and MCF-7 cell lines. The molecular docking study of most active compounds had shown good binding interactions against oxidoreductase, cyclooxygenase-1 and cyclooxygenase-2 enzymes. Conclusion: Results of in vitro anti-inflammatory, antioxidant activities and docking study showed that synthesized compounds had potential antiinflammatory and antioxidant activities and can be further optimized and developed as a lead compound.