Macrocyclic compounds as anti-cancer agents: Design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2

• DOI: 10.1016/j.ejmech.2015.03.034
• Publication Date: 2015-03-21T16:21:12Z
• Authors: Cheng-Qing Ning; Cheng Lu; Liang Hu; Yan-Jing Bi; Lei Yao; Yu-Jun He; Li-Fei Liu; Xiao-Yu Liu; Nie-Fang Yu
• Keywords: 0303 health sciences; Macrocyclic Compounds; Blotting, Western; Antineoplastic Agents; Apoptosis; Janus Kinase 2; Histone Deacetylases; 3. Good health; Histone Deacetylase Inhibitors; Molecular Docking Simulation; 03 medical and health sciences; fms-Like Tyrosine Kinase 3; Drug Design; Humans; Protein Kinase Inhibitors; Cell Proliferation; HeLa Cells; Signal Transduction

A novel series of macrocyclic compounds were designed and synthesized as multi-target inhibitors targeting HDAC, FLT3 and JAK2. Some of these compounds exhibited potent HDAC inhibition as well as FLT3 and JAK2 inhibition under both cell-free and cellular conditions. In vitro antiproliferative assay indicated that these compounds were interestingly more cytotoxic to MV4-11 cells bearing FLT3-ITD mutation and HEL cells bearing JAK2(V617F) mutation.