Discovery of new VEGFR-2 inhibitors and apoptosis inducer-based thieno[2,3- d ]pyrimidine.
Souad A El-MetwallyHazem ElkadyMuhammad A HagrasEslam B ElkaeedBshra Ali A AlsfoukAhmed S DoghishIbrahim M IbrahimMohammed S TaghourDalal Z HuseinAhmed M MetwalyIbrahim H EissaPublished in: Future medicinal chemistry (2023)
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.
Keyphrases
- vascular endothelial growth factor
- cell cycle
- molecular dynamics simulations
- cell proliferation
- cell death
- molecular docking
- oxidative stress
- endoplasmic reticulum stress
- endothelial cells
- small molecule
- drug delivery
- papillary thyroid
- human health
- transcription factor
- lymph node metastasis
- electronic health record