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

被引：12

作者：

El-Metwally, Souad A. ^{[1
]}

Elkady, Hazem ^{[2
]}

Hagras, Mohamed ^{[3
]}

Elkaeed, Eslam B. ^{[4
]}

Alsfouk, Bshra A. ^{[5
]}

Doghish, Ahmed S. ^{[6
,7
]}

Ibrahim, Ibrahim M. ^{[8
]}

Taghour, Mohammed S. ^{[2
]}

Husein, Dalal Z. ^{[9
]}

Metwaly, Ahmed M. ^{[10
,11
]}

Eissa, Ibrahim H. ^{[1
]}

机构：

[1] Higher Technol Inst, Dept Basic Sci, 10th Ramadan City, Egypt

[2] Al Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt

[3] Al Azhar Univ, Coll Pharm, Dept Pharmaceut Organ Chem, Cairo 11884, Egypt

[4] AlMaarefa Univ, Coll Pharm, Dept Pharmaceut Sci, Riyadh 13713, Saudi Arabia

[5] Princess Nourah bint Abdulrahman Univ, Coll Pharm, Dept Pharmaceut Sci, POB 84428, Riyadh 11671, Saudi Arabia

[6] Badr Univ Cairo BUC, Fac Pharm, Dept Biochem, Cairo 11829, Egypt

[7] Al Azhar Univ, Fac Pharm Boys, Biochem & Mol Biol Dept, Cairo 11231, Egypt

[8] Cairo Univ, Fac Sci, Biophys Dept, Cairo 12613, Egypt

[9] New Valley Univ, Fac Sci, Chem Dept, El Kharja 72511, Egypt

[10] Al Azhar Univ, Fac Pharm Boys, Pharmacognosy & Med Plants Dept, Cairo 11884, Egypt

[11] Genet Engn & Biotechnol Res Inst, Biopharmaceut Prod Res Dept, City Sci Res & Technol Applicat SRTA City, Alexandria, Egypt

来源：

FUTURE MEDICINAL CHEMISTRY | 2023年 / 15卷 / 22期

关键词：

apoptosis; docking; MD simulations; thieno[2,3-d]pyrimidine; VEGFR-2; IN-SILICO; MOLECULAR DOCKING; CELL-LINES; DESIGN; DERIVATIVES; TOXICITY; ADMET; ANTICANCER; VITRO; ANGIOGENESIS;

D O I：

10.4155/fmc-2023-0130

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：2065 / 2086

页数：22

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