Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies

被引：87

作者：

Taghour, Mohammed S. ^{[1
]}

Elkady, Hazem ^{[1
]}

Eldehna, Wagdy M. ^{[2
,3
]}

El-Deeb, Nehal M. ^{[4
]}

Kenawy, Ahmed M. ^{[5
]}

Elkaeed, Eslam B. ^{[6
]}

Alsfouk, Aisha A. ^{[7
]}

Alesawy, Mohamed S. ^{[1
]}

Metwaly, Ahmed M. ^{[4
,8
]}

Eissa, Ibrahim. H. ^{[1
]}

机构：

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

[2] Kafrelsheikh Univ, Dept Pharmaceut Chem, Fac Pharm, Kafrelsheikh, Egypt

[3] Badr Univ Cairo, Sch Biotechnol, Cairo, Egypt

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

[5] City Sci Res & Technol Applicat SRTA City, Genet Engn & Biotechnol Res Inst, Nucl Acids Res Dept, Alexandria, Egypt

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

[7] Princess Nourah bint Abdulrahman Univ, Coll Pharm, Dept Pharmaceut Sci, Riyadh, Saudi Arabia

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

来源：

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

关键词：

Apoptosis; anticancer; VEGFR-2; inhibitors; 2-Oxo-1; 2-dihydroquinoline; Thiazolidine-2; 4-dione; 2-Oxoindoline; ANTI-HYPERGLYCEMIC EVALUATION; RAPID COLORIMETRIC ASSAY; BIOLOGICAL EVALUATION; MOLECULAR-DYNAMICS; KINASE INHIBITORS; ANTIPROLIFERATIVE EVALUATION; QUINOXALINE DERIVATIVES; PPAR-GAMMA; BCL-XL; APOPTOSIS;

D O I：

10.1080/14756366.2022.2085693

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：

A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids with potential activity against VEGFR-2. The cytotoxic effects of the synthesised derivatives against Caco-2, HepG-2, and MDA-MB-231 cell lines were investigated. Compound 12a was found to be the most potent candidate against the investigated cell lines with IC50 values of 2, 10, and 40 mu M, respectively. Furthermore, the synthesised derivatives were tested in vitro for their VEGFR-2 inhibitory activity showing strong inhibition. Moreover, an in vitro viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. Compound 12a was further investigated for its apoptotic behaviour by assessing the gene expression of four genes (Bcl2, Bcl-xl, TGF, and Survivin). Molecular dynamic simulations authenticated the high affinity, accurate binding, and perfect dynamics of compound 12a against VEGFR-2.

引用

页码：1903 / 1917

页数：15

共 94 条

[1] Design and synthesis of novel furan, furo[2,3-d]pyrimidine and furo[3,2-e] [1,2,4]triazolo[1,5-c]pyrimidine derivatives as potential VEGFR-2 inhibitors [J].

Abd El-Mageed, Menna M. A. ;

Eissa, Amal A. M. ;

Farag, Awatef El-Said ;

Osman, Essam Eldin A. .

BIOORGANIC CHEMISTRY, 2021, 116

[2] Design and synthesis of new 4-(2-nitrophenoxy)benzamide derivatives as potential antiviral agents: molecular modeling and in vitro antiviral screening [J].

Abdallah, Abdallah E. ;

Alesawy, Mohamed S. ;

Eissa, Sally I. ;

El-Fakharany, Esmail M. ;

Kalaba, Mohamed H. ;

Sharaf, Mohamed H. ;

Abo Shama, Noura M. ;

Mahmoud, Sara H. ;

Mostafa, Ahmed ;

Al-Karmalawy, Ahmed A. ;

Elkady, Hazem .

NEW JOURNAL OF CHEMISTRY, 2021, 45 (36) :16557-16571

[3] Synthesis, Crystal Structure, and Biological Activity of cis/trans Amide Rotomers of (Z)-N′-(2-Oxoindolin-3-ylidene)formohydrazide [J].

Abdel-Aziz, Hatem A. ;

Ghabbour, Hazem A. ;

Eldehna, Wagdy M. ;

Qabeel, Maha M. ;

Fun, Hoong-Kun .

JOURNAL OF CHEMISTRY, 2014, 2014

[4] 2-Chloroquinoline-3-carbaldehyde II: Synthesis, Reactions, and Applications [J].

Abdel-Wahab, Bakr F. ;

Khidre, Rizk E. .

JOURNAL OF CHEMISTRY, 2013, 2013

[5] 1-Piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: Synthesis and in vitro biological evaluation [J].

Abou-Seri, Sahar M. ;

Eldehna, Wagdy M. ;

Ali, Mamdouh M. ;

Abou El Ella, Dalal A. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2016, 107 :165-179

[6] Discovery of new quinoxaline-based derivatives as anticancer agents and potent VEGFR-2 inhibitors: Design, synthesis, and in silico study [J].

Alanazi, Mohammed M. ;

Elkady, Hazem ;

Alsaif, Nawaf A. ;

Obaidullah, Ahmad J. ;

Alanazi, Wael A. ;

Al-Hossaini, Abdulah M. ;

Alharbi, Madhawi A. ;

Eissa, Ibrahim H. ;

Dahab, Mohammed A. .

JOURNAL OF MOLECULAR STRUCTURE, 2022, 1253

[7] New quinoxaline-based VEGFR-2 inhibitors: design, synthesis, and antiproliferative evaluation with in silico docking, ADMET, toxicity, and DFT studies [J].

Alanazi, Mohammed M. ;

Elkady, Hazem ;

Alsaif, Nawaf A. ;

Obaidullah, Ahmad J. ;

Alkahtani, Hamad M. ;

Alanazi, Manal M. ;

Alharbi, Madhawi A. ;

Eissa, Ibrahim H. ;

Dahab, Mohammed A. .

RSC ADVANCES, 2021, 11 (48) :30315-30328

[8] Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers [J].

Alanazi, Mohammed M. ;

Eissa, Ibrahim H. ;

Alsaif, Nawaf A. ;

Obaidullah, Ahmad J. ;

Alanazi, Wael A. ;

Alasmari, Abdullah F. ;

Albassam, Hussam ;

Elkady, Hazem ;

Elwan, Alaa .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2021, 36 (01) :1760-1782

[9] In Silico Screening of Semi-Synthesized Compounds as Potential Inhibitors for SARS-CoV-2 Papain-like Protease: Pharmacophoric Features, Molecular Docking, ADMET, Toxicity and DFT Studies [J].

Alesawy, Mohamed S. ;

Elkaeed, Eslam B. ;

Alsfouk, Aisha A. ;

Metwaly, Ahmed M. ;

Eissa, Ibrahim H. .

MOLECULES, 2021, 26 (21)

[10] Identification of new [1,2,4]triazolo[4,3-a]quinoxalines as potent VEGFR-2 tyrosine kinase inhibitors: Design, synthesis, anticancer evaluation, and in silico studies [J].

Alsaif, Nawaf A. ;

Taghour, Mohammed S. ;

Alanazi, Mohammed M. ;

Obaidullah, Ahmad J. ;

Alanazi, Wael A. ;

Alasmari, Abdullah ;

Albassam, Hussam ;

Dahab, Mohammed A. ;

Mahdy, Hazem A. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2021, 46

← 1 2 3 4 5 6 7 8 9 10 →