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

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

Volume: 24 Issue: 15

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

Affiliation:

• Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University, Al Takhassusi Rd, Riyadh 11533, Saudi Arabia
• Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, P.O Box 13140, Amman 11942, Jordan

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

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.

Cite this article as:

Khanfar A. Mohammad*, Salman M Ibrahim and Ameer Z Omar, Synthesis and Biological Evaluation of Thiazole-based Fibroblast Growth Factor Receptor-1 Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2024; 24 (15) . https://dx.doi.org/10.2174/1871520622666220905141248