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
收藏
页码：2065 / 2086
页数：22
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