2. Academic Validation
  3. Dihydropyrazothiazole derivatives as potential MMP-2/MMP-8 inhibitors for cancer therapy

Dihydropyrazothiazole derivatives as potential MMP-2/MMP-8 inhibitors for cancer therapy

  • Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3816-3821. doi: 10.1016/j.bmcl.2018.05.004.
Zhong-Chang Wang 1,  Fa-Qian Shen 2,  Meng-Ru Yang 2,  Ling-Xia You 3,  Li-Zhi Chen 3,  Hai-Liang Zhu 2,  Ya-Dong Lu 4,  Fan-Lei Kong 5,  Ming-Hua Wang 6
Affiliations

Affiliations

  • 1 Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Agrochem Laboratory Co., Ltd., Changzhou 213000, China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
  • 3 Jiangsu Agrochem Laboratory Co., Ltd., Changzhou 213000, China.
  • 4 Neonatal Medical Center, Children's Hospital of Nanjing Medical University, Nanjing 210008, China. Electronic address: lydawq@sina.com.
  • 5 Jiangsu Agrochem Laboratory Co., Ltd., Changzhou 213000, China. Electronic address: kongfanlei@jsmone.com.
  • 6 Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: wangmha@njau.edu.cn.
PMID: 30342958 DOI: 10.1016/j.bmcl.2018.05.004
Abstract

MMP-2/MMP-8 is established as one of the most important metalloenzymes for targeting Cancer. A series of dihydropyrazothiazole derivatives (E1-E18) bearing a salicylaldehyde group linked to Pyrazole ring were designed, synthesized, and evaluated for their pharmacological activity as MMP-2/MMP-8 inhibitors. Among them, compound E17 exhibited most potent inhibitory activity (IC50 = 2.80 μM for MMP-2 and IC50 = 5.6 μM for MMP-8), compared to the positive drug CMT-1 (IC50 = 1.29 μM). Compounds (E1-E18) were scrutinized by CoMFA and CoMSIA techniques of Three-dimensional quant. structure-activity relationship (3D-QSAR), as well as a docking simulation. Moreover, treatment with compound E4 could induce MCF-7 cell Apoptosis. Overall, the biological profile of E1-E18 may provide a research basis for the development of new agents against Cancer.

Keywords

3D-QSAR; Dihydropyrazothiazole; Docking simulation; MMP-2/MMP-8; Synthesis.

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