Elkamhawy, Ahmed Park, Jung-eun Hassan, Ahmed H. E. Pae, Ae Nim Lee, Jiyoun Paik, Sora Park, Beoung-Geon Roh, Eun Joo 2024-01-19T22:00:42Z 2024-01-19T22:00:42Z 2021-09-03 2018-09-05 0223-5234 https://pubs.kist.re.kr/handle/201004/120925 Herein, we report synthesis and evaluation of new twenty-eight pyrazinyl ureas against beta amyloid (A beta) induced opening of mitochondrial permeability transition pore (mPTP) using JC-1 assay which measures the change of mitochondrial membrane potential (Delta Psi m). The neuroprotective effect of seventeen compounds against A beta-induced mPTP opening was superior to that of the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy)pyrazin-2-yl)-3-(3,4-dichlorophenyl)urea (5) effectively maintained mitochondrial function and cell viabilities on ATP assay and MIT assay. Also, hERG channel assay presented safe cardiotoxicity profile for compound 5. In addition, using CDocker algorithm, a molecular docking model presented a plausible explanation for the elicited differences in efficiencies of the synthesized compounds to reduce the green to red fluorescence as indication of mPTP closure. Hence, this report presents compound 5 as the most promising pyrazinyl urea-based mPTP blocker up to date. (C) 2018 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER INDUCED MITOCHONDRIAL DYSFUNCTION PERMEABILITY TRANSITION PORE AMYLOID-BETA CYCLOPHILIN-D POTENT INHIBITORS DISCOVERY DERIVATIVES MODULATORS DESIGN Pyrazinyl ureas revisited: 1-(3-(Benzyloxy)pyrazin-2-yl)-3-(3,4-dichlorophenyl)urea, a new blocker of A beta-induced mPTP opening for Alzheimer's disease Article 10.1016/j.ejmech.2018.07.068 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.157, pp.268 - 278 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 157 268 278 scie scopus 000447480000020 2-s2.0-85051109966 Chemistry, Medicinal Pharmacology & Pharmacy Article INDUCED MITOCHONDRIAL DYSFUNCTION PERMEABILITY TRANSITION PORE AMYLOID-BETA CYCLOPHILIN-D POTENT INHIBITORS DISCOVERY DERIVATIVES MODULATORS DESIGN beta-amyloid peptide (A beta) Mitochondrial permeability transition pore (mPTP) A beta-induced neurotoxicity Alzheimer&apos s disease (AD) Urea Cyclophilin D