63674-74-8Relevant academic research and scientific papers
Analgesic and anticancer activity of benzoxazole clubbed 2-pyrrolidinones as novel inhibitors of monoacylglycerol lipase
Afzal, Obaid,Altamimi, Abdulmalik Saleh Alfawaz,Hassan, Md Quamrul,Riadi, Yassine,Shahroz, Mir Mohammad,Sharma, Hemant Kumar
, (2021)
Ten benzoxazole clubbed 2-pyrrolidinones (11–20) as human monoacylglycerol lipase inhibitors were designed on the criteria fulfilling the structural requirements and on the basis of previously reported inhibitors. The designed, synthesized, and characterized compounds (11–20) were screened against monoacylglycerol lipase (MAGL) in order to find potential inhibitors. Compounds 19 (4-NO2 derivative) and 20 (4-SO2 NH2 derivative), with an IC50 value of 8.4 and 7.6 nM, were found most active, respectively. Both of them showed micromolar potency (IC50 value above 50 μM) against a close analogue, fatty acid amide hydrolase (FAAH), therefore considered as selective inhibitors of MAGL. Molecular docking studies of compounds 19 and 20 revealed that carbonyl of 2-pyrrolidinone moiety sited at the oxyanion hole of catalytic site of the enzyme stabilized with three hydrogen bonds (~2 ?) with Ala51, Met123, and Ser122, the amino acid residues responsible for the catalytic function of the enzyme. Remarkably, the physiochemical and pharmacokinetic properties of compounds 19 and 20, computed by QikProp, were found to be in the qualifying range as per the proposed guideline for good orally bioactive CNS drugs. In formalin-induced nociception test, compound 20 reduced the pain response in acute and late stages in a dose-dependent manner. They significantly demonstrated the reduction in pain response, having better potency than the positive control gabapentin (GBP), at 30 mg/kg dose. Compounds 19 and 20 were submitted to NCI, USA, for anticancer activity screening. Compounds 19 (NSC: 778839) and 20 (NSC: 778842) were found to have good anticancer activity on SNB-75 cell line of CNS cancer, exhibiting 35.49 and 31.88% growth inhibition (% GI), respectively.
Pyrrolidin-2-one linked benzofused heterocycles as novel small molecule monoacylglycerol lipase inhibitors and antinociceptive agents
Altamimi, Abdulmalik Saleh Alfawaz,Bawa, Sandhya,Athar, Fareeda,Hassan, Md Quamrul,Riadi, Yassine,Afzal, Obaid
, p. 1418 - 1432 (2020/07/13)
Eighteen pyrrolidin-2-one linked benzothiazole, and benzimidazole derivatives (10–27) were designed and synthesized. The structure of the compounds was confirmed by elemental and spectral (IR, 1H-NMR and MS) data analysis. All the compounds wer
