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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2
Bioorganic and Medicinal Chemistry Letters, Volume 23, No. 9, Year 2013
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Description
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 Å), Phe 518(2.82 Å) and Arg513(2.63 and 2.73 Å). 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. © 2013 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Al-Suwaidan, Ibrahim A.
Saudi Arabia, Riyadh
College of Pharmacy
Alanazi, Amer M.
Saudi Arabia, Riyadh
College of Pharmacy
El-Azab, Adel S.
Saudi Arabia, Riyadh
College of Pharmacy
Egypt, Cairo
Faculty of Pharmacy
Al-Obaid, Abdulrahman Mohammad
Saudi Arabia, Riyadh
College of Pharmacy
ELTahir, Kamal Eldin Hussein
Saudi Arabia, Riyadh
College of Pharmacy
Maarouf, Azza R.
Egypt, Mansoura
Mansoura University
Abu El-Enin, Mohammed Abubakr
Egypt, Mansoura
Mansoura University
Abdel-Aziz, Alaa A.M.
Saudi Arabia, Riyadh
College of Pharmacy
Egypt, Mansoura
Mansoura University
Statistics
Citations: 54
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1016/j.bmcl.2013.02.107
ISSN:
0960894X
e-ISSN:
14643405