Abstract
Focal adhesion kinase (FAK) is an important drug target that plays a fundamental role in mediating signal transduction system. We report herein the discovery of a novel class of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton with improved potency toward FAK. All of the 17 new synthesized compounds were assayed for the anticancer activities against four cancer cells, HepG2, Hela, SW116 and BGC823. Because of the combination of 1,4-benzodioxan, 1,3,4-oxadiazole and piperazine ring, most of them exhibited remarkable antitumor activities. Notably, compound 5m showed the most potent biological activities (IC50=5.78μM for HepG2, and IC50=47.15μM for SW1116), and its anti-FAK inhibitory activity (IC50=0.78μM) was also the best. Computational docking studies also showed that compound 5m has interaction with FAK key residues in the active site.
Keywords:
Antitumor activity; Benzodioxan; FAK; Oxadiazoles; Piperazine.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Cell Line, Tumor
-
Dioxanes / chemical synthesis
-
Dioxanes / chemistry
-
Dioxanes / pharmacology*
-
Enzyme Assays
-
Focal Adhesion Kinase 1 / antagonists & inhibitors*
-
Humans
-
Molecular Docking Simulation
-
Oxadiazoles / chemical synthesis
-
Oxadiazoles / chemistry
-
Oxadiazoles / pharmacology*
-
Piperazines / chemical synthesis
-
Piperazines / chemistry
-
Piperazines / pharmacology*
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Structure-Activity Relationship
-
Thiones / chemical synthesis
-
Thiones / chemistry
-
Thiones / pharmacology*
Substances
-
5-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)-3-((4-(3(trifluoromethyl)phenyl)piperazin-1-yl)methyl)-1,3,4-oxadiazole-2(3H)-thione
-
Antineoplastic Agents
-
Dioxanes
-
Oxadiazoles
-
Piperazines
-
Protein Kinase Inhibitors
-
Thiones
-
Focal Adhesion Kinase 1
-
PTK2 protein, human