2. Academic Validation
  3. Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents

Discovery, bioactivity and docking simulation of Vorinostat analogues containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor agents

  • Bioorg Med Chem. 2015 Jul 1;23(13):3457-71. doi: 10.1016/j.bmc.2015.04.028.
Jin Cai 1,  Hongtao Wei 2,  Kwon Ho Hong 3,  Xiaoqing Wu 4,  Xi Zong 1,  Meng Cao 5,  Peng Wang 5,  Lushen Li 5,  Chunlong Sun 1,  Bo Chen 5,  Gaoxing Zhou 5,  Junqing Chen 1,  Min Ji 6
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.
  • 2 College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, PR China.
  • 3 Department of Medicinal Chemistry and the Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, MN 55414, USA.
  • 4 Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
  • 5 School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China.
  • 6 School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China; School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China; Suzhou Key Laboratory of Biomaterials and Technologies & Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou 215123, PR China. Electronic address: jimin@seu.edu.cn.
PMID: 25953722 DOI: 10.1016/j.bmc.2015.04.028
Abstract

In our study, three series of hydroxamate, 2-aminobenzamide, and trifluoromethyl ketone analogues have been designed and synthesized. The synthesized compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against three human Cancer cell lines including A549, NCI-H661, and U937. Most analogues exhibited higher antiproliferative activities against human acute myeloid leukemia cell U937 than the Other two human lung Cancer cell lines. Furthermore, the compounds were examined against HDAC1, 2, and 8 isoforms. Docking study of compounds 6h, 9b, and 10a suggested that they might bind tightly to the binding pocket of HDAC2 and/or HDAC8. The results suggest that these compounds might have potential as lead compounds for the development of anti-tumor drugs with HDACs inhibitory activities.

Keywords

2-Aminobenzamide; Antiproliferative activity; Docking simulation; Histone deacetylases (HDAC); Hydroxamate; Trifluoromethyl ketone.

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