Discovery of new VEGFR-2 inhibitors and apoptosis inducer-based thieno[2,3-<i>d</i>]pyrimidine-Reference-Cited by-同舟云学术

Discovery of new VEGFR-2 inhibitors and apoptosis inducer-based thieno[2,3-d]pyrimidine

Published:2023-11-13 Issue: Volume: Page:
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

El-Metwally Souad A¹^ORCID,Elkady Hazem²^ORCID,Hagras Mohamed³^ORCID,Elkaeed Eslam B⁴^ORCID,Alsfouk Bshra A⁵^ORCID,Doghish Ahmed S⁶⁷^ORCID,Ibrahim Ibrahim M⁸^ORCID,Taghour Mohammed S²^ORCID,Husein Dalal Z⁹^ORCID,Metwaly Ahmed M¹⁰¹¹^ORCID,Eissa Ibrahim H¹^ORCID

Affiliation:

1. Department of Basic Science, Higher Technological institute, 10th of Ramadan City, Egypt

2. Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt

3. Department of Pharmaceutical Organic Chemistry, College of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt

4. Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia

5. Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, PO Box 84428, Riyadh 11671, Saudi Arabia

6. Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt

7. Biochemistry & Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo 11231, Egypt

8. Biophysics Department, Faculty of Science, Cairo University, Cairo, 12613, Egypt

9. Chemistry Department, Faculty of Science, New Valley University, El-Kharja, 72511, Egypt

10. Pharmacognosy & Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt

11. Biopharmaceutical Products Research Department, Genetic Engineering & Biotechnology Research Institute, City of Scientific Research & Technological Applications (SRTA-City), Alexandria, Egypt

Abstract

Background: VEGFR-2 is a key regulator of cancer cell proliferation, migration and angiogenesis. Aim: Development of thieno[2,3- d]pyrimidine derivatives as potential anti-cancer agents targeting VEGFR-2. Methods: Seven in vitro and nine in silico studies were conducted. Results: Compound 10d demonstrated strong anticancer potential, boosting apoptosis based on VEGFR-2 inhibition. It arrested the S phase of the cell cycle and upregulated the apoptotic factors. Docking and molecular dynamics simulation studies confirm the stability of the VEGFR-2–10d complex and suggest that these compounds have good binding affinities to VEGFR-2. In addition, the drug-likeness was confirmed. Conclusion: Thieno[2,3- d]pyrimidines, particularly compound 10d, has good anticancer effects and may contribute to the development of new anticancer therapies.

Funder

Princess Nourah Bint Abdulrahman University

AlMaarefa University

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

https://www.future-science.com/doi/pdf/10.4155/fmc-2023-0130

Reference75 articles.

1. Challenges and Opportunities in Cancer Drug Resistance

2. Receptor tyrosine kinase activation: From the ligand perspective

3. Contribution of TGF-Beta-Mediated NLRP3-HMGB1 Activation to Tubulointerstitial Fibrosis in Rat With Angiotensin II-Induced Chronic Kidney Disease

4. Vascular Endothelial Growth Factor Receptor (VEGFR-2)/KDR Inhibitors: Medicinal Chemistry Perspective