Novel Pyrazole-Linked Pyran Hybrids: Synthesis, Anti-inflammatory Evaluation, Molecular Docking Studies

Abstract

In this study, a series of novel pyrazole-linked pyran hybrids was synthesized starting from 4-acetyl-1,3-diphenyl-1H-pyrazole-5(4H)-ole 1. Their structures were characterized by means of spectroscopic techniques. Further, their anti-inflammatory activities were in vitro examined using inhibition of protein denaturation, membrane stabilization assay, and quantitative real-time PCR (qRT-PCR). Compound 6 showed observed anti-inflammatory activity compared with diclofenac. Moreover, the molecular docking approach for the newly prepared hybrid molecules was also performed against phosphodiesterase 4 enzyme (PDE4) to investigate their binding modes of action. Remarkably, compound 6 exhibited the lowest binding energy (-10.8 kcal/mol) against the target. Additionally, the predicted ADMET properties of these molecules exhibited favorable drug-likeness properties.