1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies

被引：38
作者：
Hagras, Mohamed [1 ]
Saleh, Marwa A. [2 ]
Eldin, Rogy R. Ezz [3 ]
Abuelkhir, Abdelrahman A. [1 ]
Khidr, Emad Gamil [4 ]
El-Husseiny, Ahmed A. [4 ]
El-Mahdy, Hesham A. [4 ]
Elkaeed, Eslam B. [5 ]
Eissa, Ibrahim H. [6 ]
机构：
[1] Al Azhar Univ, Fac Pharm Boys, Pharmaceut Organ Chem, Cairo 11884, Egypt
[2] Al Azhar Univ, Fac Pharm Girls, Pharmaceut Organ Chem, Cairo, Egypt
[3] Port Said Univ, Fac Pharm, Dept Pharmaceut Organ Chem, Port Said, Egypt
[4] Al Azhar Univ, Fac Pharm Boys, Biochem & Mol Biol Dept, Cairo, Egypt
[5] AlMaarefa Univ, Coll Pharm, Dept Pharmaceut Sci, Riyadh, Saudi Arabia
[6] Al Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
来源：
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2022年 / 37卷 / 01期
关键词：
Anticancer; apoptosis; docking; 1; 3; 4-oxadiazole; VEGFR-2; inhibitors; ANTI-HYPERGLYCEMIC EVALUATION; RAPID COLORIMETRIC ASSAY; GROWTH-FACTOR RECEPTOR-2; BIOLOGICAL EVALUATION; ANTICANCER EVALUATION; MOLECULAR DOCKING; QUINOXALINE DERIVATIVES; KINASE INHIBITORS; RATIONAL DESIGN; PPAR-GAMMA;
D O I：
10.1080/14756366.2021.2015342
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated in vitro for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (5, 8, 15, 16, 17, and 18) were further evaluated for their VEGFR-2 inhibitory activities. Compound 5 showed good antiproliferative activity against both cell lines and inhibitory effect on VEGFR-2. Besides, it induced apoptosis by 22.86% compared to 0.51% in the control (HepG2) cells. This apoptotic effect was supported by a 5.61-fold increase in the level of caspase-3 compared to the control cells. Moreover, it arrested the HepG2 cell growth mostly at the Pre-G1 phase. Several in silico studies were performed including docking, ADMET, and toxicity studies to predict binding mode against VEGFR-2 and to anticipate pharmacokinetic, drug-likeness, and toxicity of the synthesised compounds.
引用
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页码：380 / 396
页数：17
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