These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Synthesis, anti-inflammatory activity and COX-1/COX-2 inhibition of novel substituted cyclic imides. Part 1: Molecular docking study.
    Author: Abdel-Aziz AA, ElTahir KE, Asiri YA.
    Journal: Eur J Med Chem; 2011 May; 46(5):1648-55. PubMed ID: 21388719.
    Abstract:
    A group of cyclic imides (1-13) was designed for evaluation as selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw edema model. Compounds 5b, 6b, 11b, 11c, 12b and 12c were proved to be potent COX-2 inhibitors with IC50 range of 0.1-1.0 μM. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 5b as a highly potent (IC50=0.1 μM), and an extremely selective [COX-2 (SI)=400] comparable to celecoxib [COX-2 (SI)>333.3], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50=104 mg/kg) relative to diclofenac (ED50=114 mg/kg). A Virtual screening 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. Molecular modeling (docking) study showed that the CH3O substituents of 5b inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such group underwent a H-bonding interaction with His90 (2.43, 2.83 Å), Arg513 (2.89 Å) and Tyr355 (3.34 Å). Docking study of the synthesized compound 5b into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
    [Abstract] [Full Text] [Related] [New Search]