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

Abstract

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.

• 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
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 95 Pg. 104-15 (May 05 2015) ISSN: 1768-3254 [Electronic] France
• PMID: 25800646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Macrocyclic Compounds
• Protein Kinase Inhibitors
• FLT3 protein, human
• fms-Like Tyrosine Kinase 3
• JAK2 protein, human
• Janus Kinase 2
• Histone Deacetylases

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Proliferation (drug effects)
• Drug Design
• HeLa Cells
• Histone Deacetylase Inhibitors (chemical synthesis, pharmacology)
• Histone Deacetylases (chemistry)
• Humans
• Janus Kinase 2 (antagonists & inhibitors)
• Macrocyclic Compounds (chemical synthesis, pharmacology)
• Molecular Docking Simulation
• Protein Kinase Inhibitors (chemical synthesis, pharmacology)
• Signal Transduction
• fms-Like Tyrosine Kinase 3 (antagonists & inhibitors)