Synthesis and Biological Evaluation of Novel ()--benzylidene Hydrazides As Novel C-Met Inhibitors Through Fragment Based Virtual Screening

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2020 Jan 7

PMID 31902266

Citations 1

Authors

Jing-Wei Liang

Shi-Long Li

Shan Wang

Wan-Qiu Li

Fan-Hao Meng

Affiliations

Soon will be listed here.

Abstract

C-Met plays a crucial role in the development and progression of neoplastic disease. Type II c-Met inhibitors recognise the inactive DFG-out conformation of the kinase, result in better anti-tumour effects due to synergistic effect against the other kinases. According to our previous works, an benzylidene group was selected as the initial fragment. Two series of ()--benzylidene hydrazides were designed by fragment growth method. The inhibitory activities were investigated against c-Met and VEGFR-2. Compound exhibited the most potent inhibitory activity against the c-Met inhibitor (IC = 0.37 nM). Compound exhibited multi-target c-Met kinase inhibitory activity as a potential type II c-Met inhibitor (IC = 3.41 nM against c-Met; 25.34 nM against VEGFR-2). The two compounds also demonstrate the feasibility of fragment-based virtual screening method for drug discovery.

Citing Articles

Design and biological evaluation of 3-substituted quinazoline-2,4(1,3)-dione derivatives as dual c-Met/VEGFR-2-TK inhibitors.

Hassan A, Mubarak F, Shehadi I, Mosallam A, Temairk H, Badr M J Enzyme Inhib Med Chem. 2023; 38(1):2189578.

PMID: 36919632 PMC: 10026756. DOI: 10.1080/14756366.2023.2189578.

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