دورية أكاديمية
أعرض في EDS

Discovery of novel benzofuran-based derivatives as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease: Design, synthesis, biological evaluation, molecular docking and 3D-QSAR investigation.

التفاصيل البيبلوغرافية
العنوان: Discovery of novel benzofuran-based derivatives as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease: Design, synthesis, biological evaluation, molecular docking and 3D-QSAR investigation.
المؤلفون: Abd El-Karim SS; Department of Therapeutic Chemistry, National Research Centre, P.O. Box 12262 El-Bohouth St, Cairo, Egypt. Electronic address: ssabdelkarim@gmail.com., Anwar MM; Department of Therapeutic Chemistry, National Research Centre, P.O. Box 12262 El-Bohouth St, Cairo, Egypt. Electronic address: manal.hasan52@live.com., Ahmed NS; Department of Therapeutic Chemistry, National Research Centre, P.O. Box 12262 El-Bohouth St, Cairo, Egypt., Syam YM; Department of Therapeutic Chemistry, National Research Centre, P.O. Box 12262 El-Bohouth St, Cairo, Egypt., Elseginy SA; Green Chemistry Department, Chemical Industries Research Division, National Research Centre, P. O. Box 12622, El-Bohouth St, Dokki, Cairo, Egypt., Aly HF; Department of Therapeutic Chemistry, National Research Centre, P.O. Box 12262 El-Bohouth St, Cairo, Egypt., Younis EA; Department of Therapeutic Chemistry, National Research Centre, P.O. Box 12262 El-Bohouth St, Cairo, Egypt., Khalil WKB; Department of Cell Biology, National Research Centre, P.O. Box 12262 El-Bohouth St, Dokki, Cairo, Egypt., Ahmed KA; Pathology Departments, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt., Mohammed FF; Pathology Departments, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt., Rizk M; Department of Therapeutic Chemistry, National Research Centre, P.O. Box 12262 El-Bohouth St, Cairo, Egypt.
المصدر: European journal of medicinal chemistry [Eur J Med Chem] 2023 Nov 15; Vol. 260, pp. 115766. Date of Electronic Publication: 2023 Aug 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Paris : Editions Scientifiques Elsevier
Original Publication: Paris, S.E.C.T. [etc.]
مواضيع طبية MeSH: Alzheimer Disease*/drug therapy , Benzofurans*/pharmacology, Animals ; Rats ; Cholinesterase Inhibitors/pharmacology ; Donepezil ; Acetylcholinesterase ; Molecular Docking Simulation ; Quantitative Structure-Activity Relationship ; Glutathione
مستخلص: A series of novel benzofuran-based compounds 7a-s were designed, synthesized, and investigated in vitro as acetylcholinesterase inhibitors (AChEIs). Compounds 7c and 7e displayed promising inhibitory activity with IC 50 values of 0.058 and 0.086 μM in comparison to donepezil with an IC 50 value of 0.049 μM. The new molecules' antioxidant evaluation revealed that 7c, 7e, 7j, 7n, and 7q produced the strongest DPPH scavenging activity when compared to vitamin C. As it was the most promising AChEI, compound 7c was selected for further biological evaluation. Acute and chronic toxicity studies exhibited that 7c showed no signs of toxicity or adverse events, no significant differences in the blood profile, and an insignificant difference in hepatic enzymes, glucose, urea, creatinine, and albumin levels in the experimental rat group. Furthermore, 7c did not produce histopathological damage to normal liver, kidney, heart, and brain tissues, ameliorated tissue malonaldehyde (MDA) and glutathione (GSH) levels and reduced the expression levels of the APP and Tau genes in AD rats. Molecular docking results of compounds 7c and 7e showed good binding modes in the active site of the acetylcholinesterase enzyme, which are similar to the native ligand donepezil. 3D-QSAR analysis revealed the importance of the alkyl group in positions 2 and 3 of the phenyl moiety for the activity. Overall, these findings suggested that compound 7c could be deemed a promising candidate for the management of Alzheimer's disease.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Masson SAS. All rights reserved.)
فهرسة مساهمة: Keywords: 3D-QSAR; Acetylcholinesterase inhibitors; Alzheimer's disease; Benzofuran; Donepezil; Molecular docking
المشرفين على المادة: 0 (Cholinesterase Inhibitors)
8SSC91326P (Donepezil)
EC 3.1.1.7 (Acetylcholinesterase)
0 (Benzofurans)
GAN16C9B8O (Glutathione)
تواريخ الأحداث: Date Created: 20230907 Date Completed: 20230918 Latest Revision: 20230918
رمز التحديث: 20230918
DOI: 10.1016/j.ejmech.2023.115766
PMID: 37678141
قاعدة البيانات: MEDLINE
الوصف
تدمد:1768-3254
DOI:10.1016/j.ejmech.2023.115766