Volume 35, Issue 249 (10-2025)
J Mazandaran Univ Med Sci 2025, 35(249): 3-19 |
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Makhtoumi A, Babaei R, Dabirian S, Ghasemi S. Design, synthesis, and antiproliferative activity of novel 4-anilinoquinazoline derivatives. J Mazandaran Univ Med Sci 2025; 35 (249) :3-19
URL: http://jmums.mazums.ac.ir/article-1-21690-en.html
URL: http://jmums.mazums.ac.ir/article-1-21690-en.html
Abstract: (35 Views)
Background and purpose: Inhibition of tyrosine kinases plays a crucial role in cancer treatment. Several drugs bearing an anilinoquinazoline core and acting through this mechanism have been approved by the FDA for cancer therapy. In this study, a series of new 4-anilinoquinazoline derivatives were designed, synthesized, and evaluated for their anticancer activity.
Materials and methods: Novel 4-anilinoquinazoline derivatives featuring piperidine and N, N-dimethylamine groups at the 7-position of the quinazoline core were designed, synthesized, and evaluated for their cytotoxic activity against A431, HUVEC, and HU02 cell lines. Molecular docking studies were performed to evaluate the binding interactions of the compounds with EGFR and VEGFR-2. Finally, a wound healing assay was conducted to assess the ability of the compounds to inhibit cell migration.
Results: Compounds 8d and 8f exhibited greater cytotoxicity against both cell lines compared to vandetanib (IC₅₀ = 10.62 μM for A431 and 5.75 μM for HUVEC), with IC₅₀ values of 1.99 and 2.57 μM for A431, and 3.83 and 5.64 μM for HUVEC, respectively. Compound 8d demonstrated the highest selectivity index on both cell lines (18.55 for A431 and 9.64 for HUVEC). Molecular docking studies revealed that compound 8d, bearing a 4-bromo-2-fluoro substituent at the 4-position of the quinazoline nucleus and a piperidine group at the 7-position of the quinazoline ring, exhibited stronger binding affinity to EGFR (binding energy: –8.6 kcal/mol) and VEGFR-2 (binding energy: –8.8 kcal/mol) than vandetanib. In addition, compound 8d inhibited cell migration by approximately 90%.
Conclusion: Compound 8d, which exhibited the most potent cytotoxic and anti-migratory activities, appears to be a promising lead compound for further structural optimization and biological investigation.
Materials and methods: Novel 4-anilinoquinazoline derivatives featuring piperidine and N, N-dimethylamine groups at the 7-position of the quinazoline core were designed, synthesized, and evaluated for their cytotoxic activity against A431, HUVEC, and HU02 cell lines. Molecular docking studies were performed to evaluate the binding interactions of the compounds with EGFR and VEGFR-2. Finally, a wound healing assay was conducted to assess the ability of the compounds to inhibit cell migration.
Results: Compounds 8d and 8f exhibited greater cytotoxicity against both cell lines compared to vandetanib (IC₅₀ = 10.62 μM for A431 and 5.75 μM for HUVEC), with IC₅₀ values of 1.99 and 2.57 μM for A431, and 3.83 and 5.64 μM for HUVEC, respectively. Compound 8d demonstrated the highest selectivity index on both cell lines (18.55 for A431 and 9.64 for HUVEC). Molecular docking studies revealed that compound 8d, bearing a 4-bromo-2-fluoro substituent at the 4-position of the quinazoline nucleus and a piperidine group at the 7-position of the quinazoline ring, exhibited stronger binding affinity to EGFR (binding energy: –8.6 kcal/mol) and VEGFR-2 (binding energy: –8.8 kcal/mol) than vandetanib. In addition, compound 8d inhibited cell migration by approximately 90%.
Conclusion: Compound 8d, which exhibited the most potent cytotoxic and anti-migratory activities, appears to be a promising lead compound for further structural optimization and biological investigation.
Type of Study: Research(Original) |
Subject:
Medicinal Chemistry
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