1429784-75-7Relevant academic research and scientific papers
Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2
Al-Suwaidan, Ibrahim A.,Alanazi, Amer M.,El-Azab, Adel S.,Al-Obaid, Abdulrahman M.,Eltahir, Kamal E.H.,Maarouf, Azza R.,Abu El-Enin, Mohamed A.,Abdel-Aziz, Alaa A.-M.
, p. 2601 - 2605 (2013/06/27)
A group of cyclic imides (1-10) was designed for evaluation as a selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activity. Compounds 6a, 6b, 8a, 8b, 9a, 9b, 10a and 10b were proved to be potent COX-2 inhibitors with IC50 range of 0.1-4.0 μM. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 8a as a highly potent (IC50 = 0.1 μM), and an extremely selective [COX-2 (SI) > 1000] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 72.4 mg/kg) relative to diclofenac (ED50 = 114 mg/kg). Molecular modeling was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. The study showed that the homosulfonamide fragment of 8a inserted deep inside the 2 -pocket of the COX-2 active site, where the SO2NH2 group underwent H-bonding interaction with Gln192(2.95 A?), Phe 518(2.82 A?) and Arg513(2.63 and 2.73 A?). Docking study of the synthesized compound 8a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
