Both EGFR and VEGFR-2 are important targets for cancer therapy, the combined inhibition of both EGFR and VEGFR-2 signaling pathway represents a promising approach to the treatment of cancers with a synergistic effect. In this study, a series of novel 4-anilinoquinazoline-acylamino derivatives designed as EGFR and VEGFR-2 dual inhibitors were synthesized and evaluated for biological activities. Most of them exhibited interesting inhibitory potencies against EGFR and VEGFR-2 as well as good antiproliferative activities. Compounds 15a, 15b and 15e exhibited the most potent inhibitory activity against EGFR (IC50 = 0.13 μM, 0.15 μM and 0.69 μM, respectively) and VEGFR-2 (IC50 = 0.56 μM, 1.81 μM and 0.87 μM, respectively), among them, compound 15b showed the highest antiproliferative activities against three cancer cell lines (HT-29, MCF-7 and H460) with IC50 of 5.27 μM, 4.41 μM and 11.95 μM, respectively. Molecular docking established the interaction of 15a with the DFG-out conformation of VEGFR-2, suggesting that they might be type II kinase inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2015.12.032 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis and Anticancer Evaluation of -Alkylated (-Chalcone Derivatives: A Focus on Estrogen Receptor Inhibition.
Int J Mol Sci
January 2025
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Cancer remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for novel therapeutic agents. This study investigated the synthesis and biological evaluation of -alkyl ()-chalcone derivatives (-) as potential anticancer agents. The compounds were synthesized via aldol condensation of substituted aldehydes and acetophenones, with structures confirmed by IR, NMR, and mass spectrometry.
View Article and Find Full Text PDFDual VEGFR-2 and EGFR inhibitors of phenyldiazenes: anticancer evaluations, ADMET, docking, design and synthesis.
Future Med Chem
January 2025
Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Aim: New phenyldiazene scaffold-linked heterocyclic pyrazole, pyrimidinone, pyrimidinthione, and/or triazine rings have been developed and synthesized.
Methods & Results: Cytotoxicity of our derivatives was estimated on four cancer and VERO normal cell lines targeting EGFR (epidermal growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) enzymes. Our new derivatives selectively inhibited both VEGFR-2 and EGFR as they have the essential structural requirements for inhibitors of both receptors.
Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials.
Mil Med Res
December 2024
Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam, 781039, India.
Article Synopsis
- - The prognosis for triple-negative breast cancer (TNBC) is challenging due to its heterogeneity and a lack of effective targeted therapies, prompting research into tyrosine kinases (TKs) as crucial contributors to tumor behavior and potential treatment targets.
- - Recent advancements in precision medicine have led to the exploration of various TK-targeted therapies, including monoclonal antibodies and small molecule inhibitors, that aim to combat TNBC by targeting key proteins like EGFR and VEGF.
- - The review emphasizes the importance of molecular characterization of TNBCs to maximize the effectiveness of TK-targeted therapies, indicating that treatment outcomes can significantly vary based on patient diversity.
New pyrano-pyridine conjugates as potential anticancer agents: design, synthesis and computational studies.
Future Med Chem
December 2024
Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
Article Synopsis
- * The new compounds were tested in the lab against various cancer cell lines and showed promising results, particularly compounds 8a and 8b, which had higher anticancer activity compared to the standard drug, erlotinib.
- * Compound 8a also showed effective inhibition of specific cancer-related proteins (EGFR and VEGFR-2), and additional computational studies provided insights into the compounds’ properties and how they might behave in the body.
New series of 4,6-diaryl pyrimidines: facile synthesis and antiproliferative activity as dual EGFR/VEGFR-2 inhibitors.
Front Chem
November 2024
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Article Synopsis
- - A new series of 4,6-diaryl-pyrimidines was created as potential cancer treatments that specifically target EGFR and VEGFR-2 pathways.
- - Among the synthesized compounds, two were found to be particularly effective, showing GI values of 22 and 24 nM, while also acting as dual inhibitors and promoting apoptosis in cancer cells.
- - The promising results included lower cell migration rates and superior docking scores compared to established drugs, suggesting these new compounds have great potential for further development in cancer therapy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!