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

  • Eur J Med Chem. 2015 May 5:95:104-15. doi: 10.1016/j.ejmech.2015.03.034.
Cheng-Qing Ning  1 ,  Cheng Lu  1 ,  Liang Hu  1 ,  Yan-Jing Bi  1 ,  Lei Yao  1 ,  Yu-Jun He  1 ,  Li-Fei Liu  1 ,  Xiao-Yu Liu  2 ,  Nie-Fang Yu  3
Affiliations
  • 1. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
  • 2. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China; Drug Discovery Department, Hisun Group, Taizhou 317700, China.
  • 3. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China. Electronic address: [email protected].
PMID: 25800646 DOI: 10.1016/j.ejmech.2015.03.034
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.

Keywords
FLT3; Histone deacetylase; JAK2; Macrocyclic; Multi-target inhibitor.