دورية أكاديمية
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Design, synthesis and SAR of novel 7-azaindole derivatives as potential Erk5 kinase inhibitor with anticancer activity.

التفاصيل البيبلوغرافية
العنوان: Design, synthesis and SAR of novel 7-azaindole derivatives as potential Erk5 kinase inhibitor with anticancer activity.
المؤلفون: Zhang Q; State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, China., Gao X; State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, China., Duan X; State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, China., Liang H; State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, China., Gao M; State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, China., Dong D; State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, China., Guo C; State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, China. Electronic address: gcl_cpu@126.com., Huang L; State Key Laboratory Base for Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, 266042 Qingdao, Shandong, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College, 100050 Beijing, China. Electronic address: huanglj@qust.edu.cn.
المصدر: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2023 Nov 15; Vol. 95, pp. 117503. Date of Electronic Publication: 2023 Oct 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Elsevier Science
Original Publication: Oxford : New York : Pergamon Press, c1993-
مواضيع طبية MeSH: Mitogen-Activated Protein Kinase 7*/metabolism , Antineoplastic Agents*/chemistry, Humans ; Molecular Docking Simulation ; Cell Proliferation ; Structure-Activity Relationship ; Drug Screening Assays, Antitumor ; Cell Line, Tumor ; Molecular Structure
مستخلص: The extracellular signal-regulated kinase 5 (Erk5) signaling plays a crucial role in cancer, and regulating its activity may have potential in cancer chemotherapy. In this study, a series of novel 7-azaindole derivatives (4a-5o) were designed and synthesized. Their antitumor activities on human lung cancer A549 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole (DAPI) staining and colony formation assay. Among them, compounds 4a, 4 h, 5d and 5j exhibited good anti-proliferative activity with the IC 50 values of 6.23 µg/mL, 8.52 µg/mL, 7.33 µg/mL and 4.56 µg/mL, respectively, equivalent to Erk5 positive control XMD8-92 (IC 50  = 5.36 µg/mL). The results of structure-activity relationships (SAR) showed that double bond on the piperidine ring and N atoms at the N7 position of 7-azaindole was essential for their antiproliferative activity. Furthermore, compounds 4a and 5j exhibited good inhibition on Erk5 kinase through Western blot analysis and possible action site of compounds with Erk5 kinase was elucidated by molecular docking.
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 Ltd. All rights reserved.)
فهرسة مساهمة: Keywords: 7-Azaindole; A549 cells; Anti-proliferative activity; Erk5; Molecular docking; SAR
المشرفين على المادة: 0 (7-azaindole dimer)
EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7)
0 (Antineoplastic Agents)
تواريخ الأحداث: Date Created: 20231020 Date Completed: 20231114 Latest Revision: 20231120
رمز التحديث: 20231215
DOI: 10.1016/j.bmc.2023.117503
PMID: 37862935
قاعدة البيانات: MEDLINE
الوصف
تدمد:1464-3391
DOI:10.1016/j.bmc.2023.117503