1. Dihydropyrazothiazole derivatives as potential MMP-2/MMP-8 inhibitors for cancer therapy.
- Author
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Wang ZC, Shen FQ, Yang MR, You LX, Chen LZ, Zhu HL, Lu YD, Kong FL, and Wang MH
- Subjects
- Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Apoptosis drug effects, Cell Line, Cell Line, Tumor, Drug Design, Humans, Molecular Docking Simulation, Neoplasms drug therapy, Neoplasms enzymology, Pyrazoles chemistry, Pyrazoles pharmacology, Quantitative Structure-Activity Relationship, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 8 metabolism, Matrix Metalloproteinase Inhibitors chemistry, Matrix Metalloproteinase Inhibitors pharmacology, Thiazoles chemistry, Thiazoles pharmacology
- 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 (IC
50 = 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., (Copyright © 2018. Published by Elsevier Ltd.)- Published
- 2018
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