Elkamhawy, Ahmed Lee, Jiyoun Park, Beoung-Geon Park, Insun Pae, Ae Nim Roh, Eun Joo 2024-01-20T09:01:18Z 2024-01-20T09:01:18Z 2021-09-02 2014-09-12 0223-5234 https://pubs.kist.re.kr/handle/201004/126352 A novel series of twenty-six quinazoline-urea derivatives was designed and synthesized. Their blocking activities against beta-amyloid peptide (A beta) induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measured the change of mitochondrial membrane potential. Seven compounds showed better inhibitory activities than the standard Cyclosporin A (CsA). The most active analogues were tested by MTT assay to evaluate their toxicity on the cellular survival; they revealed excellent cellular viability. To explain the difference in inhibitory activity, molecular docking study using (GOLD) program was performed for selected sets of the most active and inactive compounds on cyclophilin D (CypD) receptor as a major component of mPTP. Moreover, ADME profiling, in silico toxicity, drug-likeness, and drug-score studies were discussed. From these results, we report compound 31 as the most active nonpeptidyl mPTP blocker possessing quinazoline-urea scaffold; 2 folds of CsA activity, which would constitute a new direction for the design of novel mPTP modulators. (C) 2014 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER ALZHEIMERS-DISEASE PERMEABILITY TRANSITION AMYLOID-BETA COGNITIVE DECLINE CYCLOPHILIN DERIVATIVES DEMENTIA Novel quinazoline-urea analogues as modulators for A beta-induced mitochondrial dysfunction: Design, synthesis, and molecular docking study Article 10.1016/j.ejmech.2014.07.027 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.84, pp.466 - 475 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 84 466 475 scie scopus 000341464500043 2-s2.0-84904900475 Chemistry, Medicinal Pharmacology & Pharmacy Article ALZHEIMERS-DISEASE PERMEABILITY TRANSITION AMYLOID-BETA COGNITIVE DECLINE CYCLOPHILIN DERIVATIVES DEMENTIA Mitochondrial permeability transition pore (mPTP) Alzheimer&apos s disease (AD) Quinazoline-urea Cyclophilin D (CypD) beta-amyloid peptide (A beta) Molecular docking