Design, Synthesis and Biological Evaluation of New 1, 4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors
| Author | Iman Sabakhi | en |
| Author | Vigen Topuzyan | en |
| Author | Zahra Hajimahdi | en |
| Author | Bahram Daraei | en |
| Author | Hadi Arefi | en |
| Author | Afshin Zarghi | en |
| Issued Date | 2015-10-31 | en |
| Abstract | As a continuous research for discovery of new COX-2 inhibitors, chemical synthesis, in vitro biological activity and molecular docking study of a new group of 1, 4-dihydropyridine (DHP) derivatives were presented. Novel synthesized compounds possessing a COX-2 SO2Me pharmacophore at the para position of C-4 phenyl ring, different hydrophobic groups (R1) at C-2 position and alkoxycarbonyl groups (COOR2) at C-3 position of 1, 4-dihydropyridine, displayed selective inhibitory activity against COX-2 isozyme. Among them, compound 5e was identified as the most potent and selective COX-2 inhibitor with IC50 value of 0.30 μM and COX-2 selectivity index of 92. Molecular docking study was performed to determine probable binding models of compound 5e. The study showed that the p-SO2Me-phenyl fragment of 5e inserted inside secondary COX-2 binding site (Arg513, Phe518, Gly519, and His90). The structure-activity relationships acquired reveal that compound 5e with methyl and ethoxycarbonyl as R1 and COOR2 substitutions has the necessary geometry to provide selective inhibition of the COX-2 isozyme and it can be a good basis for the development of new hits. | en |
| DOI | https://doi.org/10.22037/ijpr.2015.1727 | en |
| Keyword | Synthesis | en |
| Keyword | 1 | en |
| Keyword | 4-Dihydropyridine (DHP) Derivatives | en |
| Keyword | COX-2 Inhibitors | en |
| Keyword | Molecular modeling | en |
| Publisher | Brieflands | en |
| Title | Design, Synthesis and Biological Evaluation of New 1, 4-Dihydropyridine (DHP) Derivatives as Selective Cyclooxygenase-2 Inhibitors | en |
| Type | Original Article | en |