Pyrazole –chalcone derivatives as selective COX-2 inhibitors: design, virtual screening, and in vitro analysis

In this study, a library of 300 pyrazole –chalcone derivatives were designed, the in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties were evaluated, and a structure-based virtual screening was performed using AutoDock Vina. The docking results exhibited that the derivatives binding mode at the COX- 2 active site is similar to celecoxib, the reference drug, and presented similar binding energy. Six compounds were synthetized and tested for in vitro inhibition of the COX-1 and COX-2 isoenzymes and the selectivity index (SI) was calculated. The compound 2a11 showed the best activity for COX-2 (IC50COX-2  = 0.73 μM) whereas the control, celecoxib, resulted IC50COX-2  = 0.88 μM. All the other compounds synthetized presented better potency for COX-2 inhibition than the control. Compound 2a23 exhibited the higher SI, of 280.17 (IC50COX-1  = 210.13 μM/ IC50COX-2  = 0.75 μM), while celecoxib was 246.88 (IC50COX-1  = 217.26 μM/ IC50COX-2  = 0.88 μM). These results corroborate with a possible anti-inflammatory activity and COX-2 selectivity of the new compounds synthetized.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research