Design, synthesis and characterization of potent microtubule inhibitors with dual anti-proliferative and anti-angiogenic activities

• Published in: European journal of medicinal chemistry Vol. 157; pp. 380 - 396
• Main Authors: Zhang, Huijun, Fang, Xiong, Meng, Qian, Mao, Yujia, Xu, Yan, Fan, Tingting, An, Jing, Huang, Ziwei
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 05.09.2018; Elsevier
• Subjects: Angiogenesis Inhibitors - chemical synthesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Anti-angiogenesis; Anti-Proliferation; Apoptosis - drug effects; Cell Cycle Checkpoints - drug effects; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemistry, Medicinal; Dose-Response Relationship, Drug; Drug Design; Drug development; Drug Screening Assays, Antitumor; Fused 4-aryl-4H-chromenes; Humans; Life Sciences & Biomedicine; Microtubule inhibitors; Microtubules - drug effects; Molecular Docking Simulation; Molecular Structure; Pharmacology & Pharmacy; Science & Technology; Structure-Activity Relationship; Tubulin - drug effects; Tubulin - metabolism; Anti-Proliferation; Anti-angiogenesis; Drug development; Fused 4-aryl-4H-chromenes; Microtubule inhibitors; COLCHICINE BINDING-SITE; SERIES; CANCER; APOPTOSIS INDUCERS; DISCOVERY; CHEMOTHERAPY; TUBULIN INHIBITORS; BIOLOGICAL EVALUATION; AGENTS; POLYALKOXY SUBSTITUTED 4H-CHROMENES

Microtubule has been an important target for anticancer drug development. Here we report the discovery and characterization of a series of fused 4-aryl-4H-chromene-based derivatives as highly potent microtubule inhibitors. Among a total of 37 derivatives synthesized, 23 exhibited strong in vitro ant...