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2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K.

التفاصيل البيبلوغرافية
العنوان: 2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K.
المؤلفون: Li ED; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Lin Q; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Meng YQ; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Zhang LY; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Song PP; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Li N; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Xin JC; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Yang P; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Bao CN; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Zhang DQ; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Zhang Y; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Wang JK; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China., Zhang QR; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China. Electronic address: zqr409@yeah.net., Liu HM; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
المصدر: European journal of medicinal chemistry [Eur J Med Chem] 2019 Jun 15; Vol. 172, pp. 36-47. Date of Electronic Publication: 2019 Mar 17.
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: Antineoplastic Agents/*pharmacology , Breast Neoplasms/*drug therapy , Phosphatidylinositol 3-Kinases/*metabolism , Protein Kinase Inhibitors/*pharmacology , Quinazolines/*pharmacology, Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; ErbB Receptors/deficiency ; ErbB Receptors/metabolism ; Female ; Humans ; Molecular Docking Simulation ; Molecular Structure ; Phosphatidylinositol 3-Kinases/deficiency ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/chemistry ; Quinazolines/chemical synthesis ; Quinazolines/chemistry ; Structure-Activity Relationship
مستخلص: A series of novel 2,4-disubstituted quinazolines were synthesized and evaluated for their anti-tumor activity against five human cancer cells (MDA-MB-231, MCF-7, PC-3, HGC-27 and MGC-803) using MTT assay. Among them, compound 9n showed the most potent cytotoxicity against breast cancer cells. Compound 9n also significantly inhibited the colony formation and migration of MDA-MB-231 and MCF-7 cells. Meanwhile, compound 9n induced cell cycle arrest at G1 phase and cell apoptosis, as well as increased accumulation of intracellular ROS. Furthermore, compound 9n exerted anti-tumor effects in vitro via decreasing the expression of anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic protein Bax and p53. Mechanistically, compound 9n markedly decreased p-EGFR and p-PI3K expression, which revealed that compound 9n targeted breast cancer cells via interfering with EGFR-PI3K signaling pathway. Molecular docking suggested that compound 9n could indeed bind into the active pocket of EGFR. All the findings suggest that compound 9n might be a valuable lead compound for anti-tumor agents targeting breast cancer cells.
(Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
فهرسة مساهمة: Keywords: Breast cancer; EGFR-PI3K; Quinazoline
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Protein Kinase Inhibitors)
0 (Quinazolines)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
EC 2.7.10.1 (EGFR protein, human)
EC 2.7.10.1 (ErbB Receptors)
تواريخ الأحداث: Date Created: 20190403 Date Completed: 20190617 Latest Revision: 20190617
رمز التحديث: 20221213
DOI: 10.1016/j.ejmech.2019.03.030
PMID: 30939352
قاعدة البيانات: MEDLINE
الوصف
تدمد:1768-3254
DOI:10.1016/j.ejmech.2019.03.030