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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Synthesis and Biological Evaluation of Thiazole-based Fibroblast Growth Factor Receptor-1 Inhibitors

Author(s): Mohammad A. Khanfar*, Ibrahim M. Salman and Omar Z. Ameer

Volume 24, Issue 15, 2024

Published on: 21 June, 2024

Page: [1159 - 1165] Pages: 7

DOI: 10.2174/1871520622666220905141248

Price: $65

Abstract

Background: The Fibroblast Growth Factor Receptor-1 (FGFR-1) is a tyrosine kinase and a validated target for the treatment of different cancer types.

Objective: Design and synthesis of novel thiazole-based analogues of anticancer agents.

Methods: Series of 2-aryl-5-methylthiazole analogues linked to structurally variable basic heads were synthesized as novel anticancer agents. Developed compounds were tested for their cytotoxic activities against several cancer cell lines.

Results: Many analogues exhibited strong antiproliferative activities against breast cancer cell lines, with higher potency towards the highly metastatic form (MDA-MB-231). Pharmacophoric profiling using an in-house pharmacophore database identified FGFR-1 as a molecular target of active analogues. Synthesized compounds were bioassayed for their FGFR-1 inhibitory activities and many hits exhibited IC50 values in the low micromolar to nanomolar range.

Conclusion: The 2-aryl-5-methylthiazole linked to a basic head is a novel chemical scaffold of ATP-competitive inhibitor of FGFR-1 with potential therapeutic activities against different types of cancer.

Keywords: thiazole, anticancer, FGFR-1, pharmacophore, kinase

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