Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti-inflammatory, antioxidant and antimicrobial agents

Abstract A novel series of 1-(2,4-dimethoxy-phenyl)-3-(1,3-diphenyl-1 H -pyrazol-4-yl)-propenone ( 3 ) have been prepared by the Claisen–Schmidt condensation of 1-(2,4-dimethoxy-phenyl)-ethanone ( 1 ) and substituted 1,3-diphenyl-1 H -pyrazole-4-carbaldehydes ( 2 ). Substituted 1,3-diphenyl-1 H -pyrazole-4-carbaldehydes ( 2 ) were prepared by Vilsmeir–Haack reaction on acetophenonephenylhydrazones to offer the target compounds. The structures of the compounds were established by IR, 1 H NMR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory (TNF-α and IL-6 inhibitory assays), antioxidant (DPPH free radical scavenging assay) and antimicrobial activities (agar diffusion method) against some pathogenic bacteria and fungi. Of 10 compounds screened, compounds 3a , 3c and 3g exhibited promising IL-6 inhibitory (35–70% inhibition, 10 μM), free radical scavenging (25–35% DPPH activity) and antimicrobial activities (MIC 100 μg/mL and 250 μg/mL) at varied concentrations. The structure–activity relationship (SAR) and in silico drug relevant properties (HBD, HBA, PSA, c  Log  P , molecular weight, E HOMO and E LUMO ) further confirmed that the compounds are potential lead compounds for future drug discovery study. Toxicity of the compounds was evaluated theoretically and experimentally and revealed to be nontoxic except 3d and 3j .