Synthesis and biological assessment of indole derivatives containing penta-heterocycles scaffold as novel anticancer agents towards A549 and K562 cells

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 38; no. 1; pp. 2163393 - 2163407
• Main Authors: Zhang, Guanglong, Tang, Zhenhua, Fan, Sili, Li, Chengpeng, Li, Yan, Liu, Weiqin, Long, Xuesha, Zhang, Wenjing, Zhang, Yi, Li, Zhurui, Wang, Zhenchao, Chen, Danping, Ouyang, Guiping
• Format: Journal Article
• Language: English
• Published: ABINGDON Taylor & Francis 01.12.2023; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: anticancer; Antineoplastic Agents; Antitumor agents; Apoptosis; Biochemistry & Molecular Biology; Bioengineering; Cancer therapies; Cell cycle; Cell Line, Tumor; Cell Proliferation; Chemistry, Medicinal; Chemotherapy; Cytotoxicity; Design; Drug Screening Assays, Antitumor; Drugs; Enzymes; Humans; Indole derivatives; Indoles; Indoles - pharmacology; K562 Cells; Leukemia; Life Sciences & Biomedicine; Lung cancer; MDM2 protein; molecular docking; Molecular Docking Simulation; Molecular Structure; penta-heterocycle; Pharmaceutical sciences; Pharmacology & Pharmacy; Prostate cancer; R&D; Research & development; Research Paper; Rubiaceae - metabolism; Science & Technology; Structure-Activity Relationship; MIGRATION; DESIGN; ACTIVATION; P53 FUNCTION; 1,3,4-OXADIAZOLE; anticancer; DISCOVERY; penta-heterocycle; EGFR INHIBITORS; PYRAZOLE; molecular docking; PATHWAY; Indole derivatives; QUINAZOLINONE DERIVATIVES
• ISSN: 1475-6366; 1475-6374; 1475-6374
• DOI: 10.1080/14756366.2022.2163393

Herein, a new series of 2-chloro-N-(5-(2-oxoindolin-3-yl)-4H-pyrazol-3-yl) acetamide derivatives containing 1,3,4-thiadiazole (10a - i) and 4H-1,2,4-triazol-4-amine (11a - r) moiety was designed, synthesised as novel anticancer agents. The antiproliferative activity values indicated that compound 10 b stood as the most potent derivative with IC 50 values of 12.0 nM and 10 nM against A549 and K562 cells, respectively. Mechanism investigation and docking studies of 10 b indicated that it possessed good apoptosis characteristic and dose-dependent growth arrest of A549 and K562 cells, blocked cell cycle into G2/M phase. Interestingly, 10 b suppressed the growth of A549 and K562 cells via modulation of EGFR and p53-MDM2 mediated pathway.