7518-98-1Relevant academic research and scientific papers
Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of phthalimide-sulfonylurea hybrids as PPARγ and SUR agonists
El-Zahabi, Mohamed Ayman,Elbendary, Eman R.,Bamanie, Faida H.,Radwan, Mohamed F.,Ghareib, Salah A.,Eissa, Ibrahim H.
, (2019/07/16)
New series of phthalimide-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds 6c, 6d, 6g, 6h, 6j and 6k induced significant reduction in the blood glucose levels of diabetic rats ranging from 24.43 to 21.43%. Moreover, molecular docking and pharmacophore approaches were carried out to examine binding modes and fit values of the prepared compounds against PPARγ and SUR, respectively. Compounds 6c, 6d, 6j and 6m exhibited the highest binding free energies against PPARγ. Compounds 6c, 6j, 6k, 6l, and 6n showed the highest fit values against the generated pharmacophore model. Also, QSAR technique was carried out to estimate the proposed PPARγ binding affinities and insulin-secreting abilities. The synthesized compounds showed promising estimated activities. In-silico ADMET studies were performed to investigate pharmacokinetics of the synthesized compounds. They showed considerable human intestinal absorption with low BBB penetration.
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.
