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Dihydropyrazothiazole derivatives as potential MMP-2/MMP-8 inhibitors for cancer therapy
Zhong-Chang Wang1, Fa-Qian Shen2, Meng-Ru Yang2
1Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Agrochem Laboratory Co., Ltd., Changzhou 213000, China.
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.
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