Anti-inflammatory Exploration of Sulfonamide Containing Diaryl Pyrazoles with Promising COX-2 Selectivity and Enhanced Gastric Safety Profilen

作者：Pavas Laxmikant S; Mane Dhananjay V^*; Baheti Kamalkishor G

来源：Journal of Heterocyclic Chemistry, 2018, 55(4): 913-922.

DOI：10.1002/jhet.3118

Novel sulfonamide containing diaryl pyrazoles were synthesized and were subsequently tested for their in vitro cyclooxygenase inhibitory assay. Compounds that showed promising in vitro COX-2 IC50 values and selectivity indices were then evaluated for their in vivo anti-inflammatory inhibition assay using standard carrageenan-induced rat paw edema method. Two promising inhibitors were evaluated for ulcerogenic liability. X-ray crystal structure of COX-2 was taken from PDB entry COX-2 (3LN1) having a resolution of 2.80 angstrom (Angstroms). Structural preparations for docking studies were accomplished using protein preparation wizard in Maestro 9.0. Compound 10b displayed reasonable COX-2 inhibition (COX-2 IC50 = 0.52 mu M) and COX-2 selectivity index (SI = 10.73) when compared with celecoxib (COX-2 IC50 = 0.78 mu M) and (SI = 9.51). In vivo anti-inflammatory studies demonstrated 64.28% inhibition for 10b in comparison with the 57.14% for that of celecoxib itself. The results of ulcerogenic liability were also found comparable with standard celecoxib. Molecular docking studies revealed that all the designed molecules showed good interactions with receptor active site with glide scores in the range -13.130 to -10.624.

• 出版日期2018-4