Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors

被引：32

作者：

Abdallah, Abdallah E. ^{[1
]}

Mabrouk, Reda R. ^{[1
]}

Al Ward, Maged Mohammed Saleh ^{[1
]}

Eissa, Sally, I ^{[2
,3
]}

Elkaeed, Eslam B. ^{[3
]}

Mehany, Ahmed B. M. ^{[4
]}

Abo-Saif, Mariam A. ^{[5
]}

El-Feky, Ola A. ^{[5
]}

Alesawy, Mohamed S. ^{[1
]}

El-Zahabi, Mohamed Ayman ^{[1
]}

机构：

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

[2] Al Azhar Univ, Fac Pharm Girls, Dept Pharmaceut Chem, Cairo, Egypt

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

[4] Al Azhar Univ, Fac Sci, Zool Dept, Cairo, Egypt

[5] Tanta Univ, Fac Pharm, Biochem Dept, Tanta, Egypt

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2022年 / 37卷 / 01期

关键词：

Anticancer; apoptosis; multi-kinase; pharmacophoric features; VEGFR-2; KINASE INHIBITORS; DISCOVERY; CANCER; DERIVATIVES; MECHANISMS; BINDING;

D O I：

10.1080/14756366.2021.2017911

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：

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC50 values ranged from 60.00 to 123.85 nM for the new derivatives compared to 54.00 nM for sorafenib. Compounds 15(a) , 15(b) , and 15(d) showed IC50 from 17.39 to 47.10 mu M against human cancer cell lines; hepatocellular carcinoma (HepG2), prostate cancer (PC3), and breast cancer (MCF-7). Meanwhile, the first in terms of VEGFR-2 inhibition was compound 15(d) which came second with regard to antitumor assay with IC50 = 24.10, 40.90, and 33.40 mu M against aforementioned cell lines, respectively. Furthermore, Compound 15(d) increased apoptosis rate of HepG2 from 1.20 to 12.46% as it significantly increased levels of Caspase-3, BAX, and P53 from 49.6274, 40.62, and 42.84 to 561.427, 395.04, and 415.027 pg/mL, respectively. Moreover, 15(d) showed IC50 of 253 and 381 nM against HER2 and FGFR, respectively.

引用

页码：573 / 591

页数：19

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