Details

Autor(en) / Beteiligte

• Wang, Zhong-Chang
• Shen, Fa-Qian
• Yang, Meng-Ru
• You, Ling-Xia
• Chen, Li-Zhi
• Zhu, Hai-Liang
• Lu, Ya-Dong
• Kong, Fan-Lei
• Wang, Ming-Hua

Titel

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

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2018-12, Vol.28 (23-24), p.3816-3821

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2018

Quelle

ScienceDirect

Beschreibungen/Notizen

• Interactions between compound E16 and MMP-2 in a three dimentional stereogram. [Display omitted] •18 Dihydropyrazothiazole derivatives had been synthesized.•Most of the compounds showed low toxicity to 293T/LO2 cells.•Compound E17 showed the most potent and best selective MMP-2 inhibition.•We built a 3D-QASR model for the further explanation of SAR about these compounds. 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.