Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti-inflammatory, antioxidant and antimicrobial agents.
A novel series of 1-(2,4-dimethoxy-phenyl)-3-(1,3-diphenyl-1H-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-1H-pyrazole-4-carbaldehydes (2). Substituted 1,3-diphenyl-1H-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-alpha 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 microM), free radical scavenging (25-35% DPPH activity) and antimicrobial activities (MIC 100 microg/mL and 250 microg/mL) at varied concentrations. The structure-activity relationship (SAR) and in silico drug relevant properties (HBD, HBA, PSA, cLogP, 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.
Bandgar
Babasaheb P
BP
Organic Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, India. bandgar_bp@yahoo.com
Gawande
Shrikant S
SS
Bodade
Ragini G
RG
Gawande
Nalini M
NM
Khobragade
Chandrahasya N
CN
D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D047188:Chalcones; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors