- Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: Anti-inflammatory and analgesic activities
-
A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 Combining double low line 0.18, 0.24, 0.28 and 0.36 μM; respectively) and selectivity index (SI) range of 363-668. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 6a as a highly potent (IC50 Combining double low line 0.18 μM), and an extremely selective [COX-2 (SI) Combining double low line 668] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 Combining double low line 54.0 mg/kg) relative to diclofenac (ED50 Combining double low line 114 mg/kg). Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His90 (3.02 g.,), Arg513 (1.94, 2.83 g.,), and Gln192 (3.25 g.,).
- Alanazi, Amer M.,El-Azab, Adel S.,Al-Suwaidan, Ibrahim A.,Eltahir, Kamal Eldin H.,Asiri, Yousif A.,Abdel-Aziz, Naglaa I.,Abdel-Aziz, Alaa A.-M.
-
p. 115 - 123
(2015/02/19)
-
- A new series of N2-substituted-5-(p-toluenesulfonylamino)phthalimide analogues as α-glucosidase inhibitors
-
Several members of a new family of non-sugar-type α-glycosidase inhibitors, bearing a 5-(p-toluenesulfonylamino)phthalimide moiety and various substituent at the N2 position, were synthesized and their activities were investigated. The newly synthesized compounds displayed different inhibition profile towards yeast α-glycosidase and rat intestinal α-glycosidase. Almost all the compounds had strong inhibitory activities against yeast α-glycosidase. Regarding rat intestinal α-glycosidase, only analogs with N2-aromatic substituents displayed varying degrees of inhibitory activities on rat intestinal maltase and lactase and nearly all compounds showed no inhibition against rat intestinal α-amylase. Structure-activity relationship studies indicated that 5-(p- toluenesulfonylamino)phthalimide moiety is a favorable scaffold to exert the α-glucosidase inhibitory activity and substituents at the N2 position have considerable influence on the efficacy of the inhibition activities.
- Bian, Xiaoli,Wang, Qian,Ke, Changhu,Zhao, Guilan,Li, Yiping
-
p. 2022 - 2026
(2013/04/24)
-