Thiazole-Derived Dual EGFR/CDK-2 Inhibitors: Rational Design, Synthesis, In Vitro Anticancer Evaluation, Mechanistic
Rowida Nasr1, Mohamed S Nafie2,3, Hesham Haffez4,5
1Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Archiv Der Pharmazie
|July 17, 2026
Summary
New thiazole compounds show potent anticancer activity against HCT-116 and MCF-7 cell lines. Lead compounds 14d, 14h, and 14i inhibit EGFR and CDK-2 kinases, inducing apoptosis and cell cycle arrest.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Molecular Biology
Background:
- Developing novel anticancer agents is crucial for effective cancer therapy.
- Thiazole derivatives have shown promise as anticancer agents.
- Targeting specific kinases like EGFR and CDK-2 is a key strategy in cancer treatment.
Purpose of the Study:
- To design, synthesize, and evaluate novel thiazole analogues for anticancer activity.
- To investigate the inhibitory potential of lead compounds against EGFR and CDK-2.
- To elucidate the mechanism of action of promising thiazole derivatives.
Main Methods:
- Synthesis and biological evaluation of thiazole analogues against HCT-116 and MCF-7 cancer cell lines.
- In vitro kinase inhibition assays against EGFR and CDK-2.
- Apoptosis induction, cell cycle analysis, Western blotting, network pharmacology, molecular docking, and molecular dynamics simulations.
- In silico ADMET and drug-likeness profiling.
Main Results:
- Compounds 14d, 14h, and 14i demonstrated significant anticancer activity against HCT-116 cells.
- Compound 14i potently inhibited EGFR (IC50=0.056 µM) and CDK-2 (IC50=0.215 µM).
- These compounds induced apoptosis and G2/M cell cycle arrest, modulated pro-apoptotic and anti-apoptotic proteins, and showed favorable in silico drug properties.
Conclusions:
- The synthesized thiazole analogues represent promising lead compounds for anticancer drug development.
- Compound 14i exhibits potent dual inhibition of EGFR and CDK-2, suggesting a potential therapeutic strategy.
- Further optimization and mechanistic studies are warranted to validate these findings.
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