Title

Modification and Biological Evaluation of Thiazole Derivatives as Novel Inhibitors of Metastatic Cancer Cell Migration and Invasion

Authors

Shilong Zheng, Xavier University of LouisianaFollow
Qiu Zhong, Xavier University of LouisianaFollow
Y. xi, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 600041, China
M Mottamal, Xavier University of LouisianaFollow
Q Zhang, Xavier University of LouisianaFollow
R. L. Schroede, Xavier University of Louisiana
Jayalakshmi Sridhar, Xavier University of LouisianaFollow
L. He, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 600041, China
H. McFerrin, Xavier University of LouisianaFollow
Guangdi Wang, Xavier University of LouisianaFollow

Funding Source

NIH-NIMHD, NIH-NIGMS, Louisiana Cancer Research Consortium

Grant Number

8G12MD007595, 8P20GM103424, P20RR016456

Department

Department of Chemistry

Document Type

Article

Publication Date

8-14-2014

Abstract

Fascin has recently emerged as a potential therapeutic target, as its expression in cancer cells is closely associated with tumor progression and metastasis. Following the initial discovery of a series of thiazole derivatives that demonstrated potent antimigration and antiinvasion activities via possible inhibition of fascin function, we report here the design and synthesis of 63 new thiazole derivatives by further structural modifications in search of more potent fascin inhibitors. The 5 series of analogues with longer alkyl chain substitutions on the thiazole nitrogen exhibited greater antimigration activities than those with other structural motifs. The most potent analogue, 5p, inhibited 50% of cell migration at 24 nM. Moreover, the thiazole analogues showed strong antiangiogenesis activity, blocking new blood vessel formation in a chicken embryo membrane assay. Finally, a functional study was conducted to investigate the mechanism of action via interaction with the F-actin bundling protein fascin.

Comments

DOI: 10.1021/jm500724x

PubMed ID: 25007006

Acknowledgement

This work was supported by NIH-NIMHD through Grant 8G12MD007595 and NIH-NIGMS through Grants 8P20GM103424 and P20RR016456 and in part by Louisiana Cancer Research Consortium. We thank Thomas Vu, Bria Carmichael, Briana Jarrett, Sydnie Turner, Eric Stewart, and Elise LeMelle for technical assistance in the CAM assays.

ACS Open Access

Recommended Citation

Zheng, Shilong; Zhong, Qiu; xi, Y.; Mottamal, M; Zhang, Q; Schroede, R. L.; Sridhar, Jayalakshmi; He, L.; McFerrin, H.; and Wang, Guangdi, "Modification and Biological Evaluation of Thiazole Derivatives as Novel Inhibitors of Metastatic Cancer Cell Migration and Invasion" (2014). Faculty and Staff Publications. 152.
https://digitalcommons.xula.edu/fac_pub/152