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Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
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Multi-Kinase Inhibition by New Quinazoline-Isatin Hybrids: Design, Synthesis, Biological Evaluation and Mechanistic
Mohammed M Alanazi1, Reem I Al-Wabli1
1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Pharmaceuticals (Basel, Switzerland)
|October 29, 2025
Summary
A novel isatin-quinazoline hybrid, compound 6c, demonstrates potent anticancer activity by inhibiting multiple kinases and inducing apoptosis. This compound shows promise as a therapeutic agent for cancer treatment.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Pharmacology
Background:
- Cancer remains a leading global cause of death, necessitating the development of novel anticancer agents.
- Protein kinases are validated targets for anticancer drug development.
- Isatin-quinazoline hybrids represent a class of compounds with potential therapeutic applications.
Purpose of the Study:
- To synthesize and evaluate a series of isatin-quinazoline hybrids as potential anticancer agents.
- To identify specific molecular targets and mechanisms of action for active compounds.
- To assess the therapeutic potential of lead compounds through in vitro assays and molecular simulations.
Main Methods:
- Synthesis of isatin-quinazoline hybrids.
- In vitro antiproliferative activity assessment using MTT assays against HepG2, MCF-7, MDA-MB-231, and HeLa cancer cell lines, and WI38 normal fibroblasts.
- Apoptosis induction analysis via Western blotting for Bcl-2, Bax, caspase-3, caspase-9, and Annexin V-FITC/PI staining.
- Cell cycle analysis using flow cytometry.
- In vitro kinase inhibition assays against CDK2, EGFR, VEGFR-2, and HER2.
- Molecular docking simulations against CDK2.
Main Results:
- Compound 6c exhibited significant antiproliferative activity across all tested cancer cell lines.
- Compound 6c induced apoptosis, evidenced by altered expression of apoptosis-related proteins and Annexin V/PI staining.
- Flow cytometry revealed that compound 6c causes cell cycle arrest at the sub-G1 and S phases in HepG2 cells.
- Compound 6c demonstrated potent multi-kinase inhibitory activity against CDK2, EGFR, VEGFR-2, and HER2 (IC50 values ranging from 0.076 to 0.183 μM).
- Molecular docking supported the binding interactions of compound 6c with the CDK2 active site.
Conclusions:
- Compound 6c is a potent multi-kinase inhibitor with significant anticancer properties.
- The mechanism of action involves the induction of apoptosis and cell cycle arrest.
- Compound 6c represents a promising lead candidate for further development as an anticancer therapeutic agent.
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