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


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Abstract

Background:The Fibroblast Growth Factor Receptor-1 (FGFR-1) is a tyrosine kinase and a validated target for 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.

About the authors

Mohammad Khanfar

Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University

Author for correspondence.
Email: info@benthamscience.net

Ibrahim Salman

Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University,

Email: info@benthamscience.net

Omar Ameer

Al Takhassusi Rd, Riyadh 11533, Alfaisal University,

Email: info@benthamscience.net

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