Discovery of New VEGFR-2 Inhibitors and Apoptosis inducer-based thieno[2,3- d ]pyrimidine

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 demonst...

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Published in:Future medicinal chemistry 2023-11, Vol.15 (22), p.2065-2086
Main Authors: El-Metwally, Souad A, Elkady, Hazem, Hagras, Mohamed, Elkaeed, Eslam B, Alsfouk, Bshra A, Doghish, Ahmed S, Ibrahim, Ibrahim M, Taghour, Mohammed S, Husein, Dalal Z, Metwaly, Ahmed M, Eissa, Ibrahim H
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container_end_page 2086
container_issue 22
container_start_page 2065
container_title Future medicinal chemistry
container_volume 15
creator El-Metwally, Souad A
Elkady, Hazem
Hagras, Mohamed
Elkaeed, Eslam B
Alsfouk, Bshra A
Doghish, Ahmed S
Ibrahim, Ibrahim M
Taghour, Mohammed S
Husein, Dalal Z
Metwaly, Ahmed M
Eissa, Ibrahim H
description 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.
doi_str_mv 10.4155/fmc-2023-0130
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title Discovery of New VEGFR-2 Inhibitors and Apoptosis inducer-based thieno[2,3- d ]pyrimidine
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