Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and In Vitro Cytotoxicity

被引：0
|
作者：
Abd El-Haleem, Akram H. [1 ]
Kassem, Manar Abd El-karim [1 ]
Elnagar, Mohamed R. [2 ,3 ]
Abbas, Safinaz E-S. [4 ]
El Kerdawy, Ahmed M. [4 ,5 ]
Farouk, Ahmed K. B. A. W. [4 ]
机构：
[1] Misr Univ Sci & Technol, Coll Pharmaceut Sci & Drug Mfg, Pharmaceut Chem Dept, Giza 77, Egypt
[2] Al Azhar Univ, Fac Pharm, Pharmacol & Toxicol Dept, Cairo 11823, Egypt
[3] Islamic Univ, Coll Pharm, Dept Pharmacol, Najaf 54001, Iraq
[4] Cairo Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11562, Egypt
[5] Univ Lincoln, Coll Hlth & Sci, Sch Hlth & Care Sci, Lincoln LN6 7DL, Lincs, England
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2024年 / 15卷 / 12期
关键词：
Furan; Furopyrimidine; VEGFR-2; Cytotoxicity; Sorafenib; A549; HT-29; KINASE INHIBITORS; THERAPY; CANCER;
D O I：
10.1021/acsmedchemlett.4c00438
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
New derivatives 4a-d, 6, 7a-d, 8a-c, 9, 11a, 11b, 12a-f, 13a-c, and 14 were synthesized and evaluated for their VEGFR-2 inhibition. Compounds 4c, 7b, and 7c showed remarkable enzyme inhibition (IC50 = 57.1, 42.5, and 52.5 nM, respectively) relative to sorafenib (IC50 = 41.1 nM) and were assessed for their cytotoxicity versus HepG2, MCF-7, A549, HT-29, and PC3 cancer cell lines in addition to WI-38. Compound 7b displayed nearly equipotent cytotoxicity against A549 and HT-29 (IC50 = 6.66 and 8.51 mu M) compared to sorafenib (IC50 = 6.60 and 8.78 mu M). Cell cycle analysis and apoptotic assay of 7b in the HT-29 cell line showed cellular growth arrest at the G2/M phase in addition to the induction of apoptosis. Western blot analysis of compound 7b revealed the deactivation of VEGFR-2. Moreover, a wound healing assay of 7b showed inhibition of wound closure. Additionally, molecular modeling studies of compounds 4c, 7b, and 7c were carried out.
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收藏
页码：2150 / 2157
页数：8
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