دورية أكاديمية
Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy.
| العنوان: | Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy. |
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| المؤلفون: | Ibrahim TS; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt. Electronic address: tmabrahem@kau.edu.sa., Hawwas MM; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt., Taher ES; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt., Alhakamy NA; Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Alfaleh MA; Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Elagawany M; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt., Elgendy B; Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO 63110, USA; Center for Clinical Pharmacology, Washington University School of Medicine and St. Louis College of Pharmacy, St. Louis, MO 63110, USA; Chemistry Department, Faculty of Science, Benha University, Benha 13518, Egypt., Zayed GM; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University at Assiut, Assiut, Egypt; Al-Azhar Centre of Nanosciences and Applications (ACNA), Assiut, Egypt., Mohamed MFA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524 Sohag, Egypt., Abdel-Samii ZK; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt., Elshaier YAMM; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, 32958 Menoufia, Egypt. |
| المصدر: | Bioorganic chemistry [Bioorg Chem] 2020 Dec; Vol. 105, pp. 104352. Date of Electronic Publication: 2020 Oct 08. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| مواضيع طبية MeSH: | Antineoplastic Agents/*chemical synthesis , Phosphodiesterase 5 Inhibitors/*chemical synthesis , Quinolines/*chemical synthesis, Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Caspases, Effector/metabolism ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cytochromes c/metabolism ; Drug Design ; Drug Screening Assays, Antitumor ; ErbB Receptors/antagonists & inhibitors ; Humans ; Molecular Docking Simulation ; Molecular Structure ; Phosphodiesterase 5 Inhibitors/pharmacology ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Quinolines/pharmacology ; bcl-2-Associated X Protein/metabolism |
| مستخلص: | PDE5 targeting represents a new and promising strategy for apoptosis induction and inhibition of tumor cell growth due to its over-expression in diverse types of human carcinomas. Accordingly, we report the synthesis of series of pyrazolo[3,4-d]pyrimidin-4-one carrying quinoline moiety (11a-r) with potential dual PDE5 inhibition and apoptotic induction for cancer treatment. These hybrids were structurally elucidated and characterized with variant spectroscopic techniques as 1 H NMR, 13 C NMR and elemental analysis. The assessment of their anticancer activities has been declared. All the rationalized compounds 11a-r have been selected for their cytotoxic activity screening by NCI against 60 cell lines. Compounds 11a, 11b, 11j and 11k were the most active hybrids. Among all, compound 11j was further selected for five dose tesing and it displayed outstanding activity with strong antitumor activity against the nine tumor subpanels tested with selectivity ratios ranging from 0.019 to 8.3 at the GI (Copyright © 2020 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Anticancer; Apoptotic inducers; Molecular docking; PDE5 inhibitors; Pyrazolo[3,4-d]pyrimidine; Quinoline |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Phosphodiesterase 5 Inhibitors) 0 (Protein Kinase Inhibitors) 0 (Proto-Oncogene Proteins c-bcl-2) 0 (Quinolines) 0 (bcl-2-Associated X Protein) 9007-43-6 (Cytochromes c) EC 2.7.10.1 (ErbB Receptors) EC 3.4.22.- (Caspases, Effector) |
| تواريخ الأحداث: | Date Created: 20201020 Date Completed: 20210319 Latest Revision: 20210319 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.bioorg.2020.104352 |
| PMID: | 33080494 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2020.104352 |