title: Discovery of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives as novel VEGFR-2 kinase inhibitors.
abstract: Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. In this work, a series of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives were designed and identified as potent inhibitors of VEGFR-2 (KDR) kinase. These compounds with quinoline scaffold and benzimidazole moiety were synthesized and their biological activities against VEGFR-2 and two human cancer cell lines were evaluated. Among them, compound 7s exhibited the most potent inhibitory activity against VEGFR-2 with IC50 of 0.03 μM and it also showed the highest anticancer activity against the tested cancer cell lines with IC50 of 1.2 μM against MCF-7 and 13.3 μM against Hep-G2. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of VEGFR-2, which demonstrates that compound 7s is a potential agent for cancer therapy deserving further researching.
authors: Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: shilei@cpu.edu.cn.
authors: Lei
authors: L
authors: Shi
authors: Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Ting-Ting
authors: TT
authors: Wu
authors: Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Zhi
authors: Z
authors: Wang
authors: Jiangsu Provincial Key Laboratory for Plant Ex Situ Conservation, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, PR China.
authors: Jia-Yu
authors: JY
authors: Xue
authors: Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: xyg@cpu.edu.cn.
authors: Yun-Gen
authors: YG
authors: Xu
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D001562:Benzimidazoles; C000596764:N-(2-(3,4-dichlorophenyl)-1H-benzo(d)imidazol-6-yl)quinolin-4-amine; D047428:Protein Kinase Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Antitumor; Benzimidazole; Quinolin; VEGFR-2 kinase inhibitor