Medicinal Chemistry Research

, Volume 24, Issue 5, pp 1814–1829 | Cite as

Synthesis and biological evaluation of novel 1,2-benzisothiazol-3-one-derived 1,2,3-triazoles as caspase-3 inhibitors

  • Zhenfei Guo
  • Zhihui Yan
  • Xiaowei Zhou
  • Quan Wang
  • Meiqi Lu
  • Wei LiuEmail author
  • Honggang Zhou
  • Cheng Yang
  • Edward J. McClain
Original Research


Several series of novel 1,4-disubstituted 1,2,3-triazoles were prepared using the Huisgen cycloaddition reaction and evaluated as inhibitors against caspase-3/-7. The 1,2-benzisothiazol-3-one-derived 1,4-disubstituted 1,2,3-triazoles containing an urea group had dramatically increased inhibitory activity in vitro compared to the others, and the most potent caspase-3 inhibitor was found to be N-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-3-oxobenzoisothiazole-2(3H)-carboxamide 14c with IC50-values of 11.0 ± 1.2 nM. Meanwhile, the compound 14c showed significant protection against apoptosis in human Jurkat T cells, as determined by annexin V-FITC/7-AAD. Moreover, in order to better rationalize the action and the binding mode of these compounds, docking studies were carried out.


Caspase-3 inhibitor 1,2,3-Triazoles 1,2-Benzisothiazol-3-one Apoptosis Docking studies 



This work was supported by the National Natural Science Foundation of China (Grant No. 21302139).


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Zhenfei Guo
    • 2
  • Zhihui Yan
    • 2
  • Xiaowei Zhou
    • 2
  • Quan Wang
    • 3
  • Meiqi Lu
    • 3
  • Wei Liu
    • 1
    Email author
  • Honggang Zhou
    • 4
  • Cheng Yang
    • 4
    • 5
  • Edward J. McClain
    • 6
  1. 1.College of SciencesTianjin University of Science and TechnologyTianjinChina
  2. 2.College of BiotechnologyTianjin University of Science and TechnologyTianjinChina
  3. 3.College of Life SciencesNanKai UniversityTianjinChina
  4. 4.College of PharmacyNanKai UniversityTianjinChina
  5. 5.High Throughput Molecular Drug Discovery CenterTianjin International Joint Academy of Biotechnology and Medicine, TEDATianjinChina
  6. 6.C. Eugene Bennett Department of ChemistryWest Virginia UniversityMorgantownUSA

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