Design, Synthesis, and Anticancer Activities of Novel 2-Amino-4-phenylthiazole Scaffold Containing Amide Moieties

Zhi-Hua Zhang,Muriira Cyrus Mwenda,Dong Cai,Yu Chen,Hong-Mei Wu,Xiao-Yu Cai,Jin-Yin Wang,Yu Yao,Sai-Nan Deng

doi:10.1155/2018/4301910

Abstract

Appropriately substituted 2-amino-4-phenylthiazole derivatives were designed and synthesized according to the structural characteristics of crizotinib. The obtained compounds were characterized using 1H NMR, 13C NMR, and HRMS. The target compounds 5a–o were evaluated for their in vitro antiproliferative activity against A549, HeLa, HT29, and Karpas299 human cancer cell lines. Based on results of biological studies, some of these compounds exhibited significant antiproliferative activity. Compound 5b possessed outstanding growth inhibitory effects on the four cell lines, especially for HT29 cell with IC50 value of 2.01 µM. Along with the biological assay data, a molecular docking study suggests that the target compounds were a potential inhibitor.

Highlights

To design a novel scaffold of c-Met inhibitor (Figure 2(b)), a bioactive 2-amino-4-phenylthiazole scaffold was used as the skeleton
General Synthesis of the Target Compounds. e synthetic route of the target compounds in the current work is depicted in Scheme 1. 2-Bromo-1-(3-nitrophenyl)ethanone was warmed with thiourea in ethanol to obtain compound 1 in a good yield. e amino moiety of compound 1 was Nacylated with the excess chloroacetyl chloride in dichloromethane at room temperature to yield compound 2
The phenyl ring 2 (Figure 2(b)) of compound 5b faced the solvent accessible region, similar to the hydrophobic 4-(1H-pyrazol-1-yl)piperidine moiety of crizotinib, which may explain the cause of slightly worse antiproliferative activity of the target compounds

Summary

Introduction

To design a novel scaffold of c-Met inhibitor (Figure 2(b)), a bioactive 2-amino-4-phenylthiazole scaffold was used as the skeleton. The phenyl ring 2 (Figure 2(b)) of compound 5b faced the solvent accessible region, similar to the hydrophobic 4-(1H-pyrazol-1-yl)piperidine moiety of crizotinib, which may explain the cause of slightly worse antiproliferative activity of the target compounds.

Results

Conclusion