Discovery of new quinoxaline-based derivatives as anticancer agents and potent VEGFR-2 inhibitors: Design, synthesis, and in silico study DOI
Mohammed M. Alanazi, Hazem Elkady, Nawaf A. Alsaif

et al.

Journal of Molecular Structure, Journal Year: 2021, Volume and Issue: 1253, P. 132220 - 132220

Published: Dec. 18, 2021

Language: Английский

Angiogenic signaling pathways and anti-angiogenic therapy for cancer DOI Creative Commons

Zhenling Liu,

Huanhuan Chen,

Lili Zheng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 11, 2023

Abstract Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- anti-angiogenic molecules, which plays crucial role in tumor growth, invasion, metastasis. With advances molecular cellular biology, biomolecules such as growth factors, chemokines, adhesion factors involved angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules driven treatment to become promising strategy anti-tumor therapy. The most widely used agents include monoclonal antibodies tyrosine kinase inhibitors (TKIs) targeting vascular endothelial factor (VEGF) pathway. However, clinical benefit this modality still limited due several defects adverse events, acquired drug resistance, recurrence, lack validated biomarkers, impel further mechanisms angiogenesis, development multiple drugs combination therapy figure out how improve efficacy. Here, we broadly summarize signaling pathways discuss current challenges We also propose approaches efficacy provide perspective for

Language: Английский

Citations

483
New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies DOI Creative Commons
Hazem Elkady, Alaa Elwan, Hesham A. El-Mahdy

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 37(1), P. 403 - 416

Published: Dec. 27, 2021

A new series of benzoxazole derivatives were designed and synthesised to have the main essential pharmacophoric features VEGFR-2 inhibitors. Cytotoxic activities evaluated for all against two human cancer cell lines, MCF-7 HepG2. Also, effect most cytotoxic on protein concentration was assessed by ELISA. Compounds

Language: Английский

Citations

112
Discovery of novel pyrazole based Urea/Thiourea derivatives as multiple targeting VEGFR-2, EGFRWT, EGFRT790M tyrosine kinases and COX-2 Inhibitors, with anti-cancer and anti-inflammatory activities DOI

Wael A.A. Fadaly,

Mohamed T. M. Nemr,

Nesma M. Kahk

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 147, P. 107403 - 107403

Published: April 27, 2024

Language: Английский

Citations

17
Discovery of new quinoxaline-2(1H)-one-based anticancer agents targeting VEGFR-2 as inhibitors: Design, synthesis, and anti-proliferative evaluation DOI
Khaled El‐Adl,

Helmy Sakr,

Reda G. Yousef

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 114, P. 105105 - 105105

Published: June 18, 2021

Language: Английский

Citations

85
New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: Design, molecular modeling, and synthesis DOI
Nawaf A. Alsaif, Mohammed A. Dahab, Mohammed M. Alanazi

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 110, P. 104807 - 104807

Published: March 6, 2021

Language: Английский

Citations

83
New bis([1,2,4]triazolo)[4,3-a:3′,4′-c]quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer evaluation DOI
Mohammed M. Alanazi,

Hazem A. Mahdy,

Nawaf A. Alsaif

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 112, P. 104949 - 104949

Published: April 30, 2021

Language: Английский

Citations

77
Design, synthesis, molecular docking, in silico ADMET profile and anticancer evaluations of sulfonamide endowed with hydrazone-coupled derivatives as VEGFR-2 inhibitors DOI

Asmaa M. Sayed,

Fatma A. Taher,

Mohammad Abdel-Samad

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 108, P. 104669 - 104669

Published: Jan. 21, 2021

Language: Английский

Citations

65
Discovery of new quinolines as potent colchicine binding site inhibitors: design, synthesis, docking studies, and anti-proliferative evaluation DOI Creative Commons
Mohamed Hagras, Moshira A. El Deeb, Heba S. A. Elzahabi

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 36(1), P. 640 - 658

Published: Jan. 1, 2021

Discovering of new anticancer agents with potential activity against tubulin polymerisation is still a promising approach. Colchicine binding site inhibitors are the most relevant anti-tubulin agents. Thus, quinoline derivatives have been designed and synthesised to possess same essential pharmacophoric features colchicine inhibitors. The compounds were tested in vitro panel three human cancer cell lines (HepG-2, HCT-116, MCF-7) using as positive control. Comparing (IC50 = 7.40, 9.32, 10.41 µM HepG-2, MCF-7, respectively), 20, 21, 22, 23, 24, 25, 26, 28 exhibited superior cytotoxic activities IC50 values ranging from 1.78 9.19 µM. In order sightsee proposed mechanism anti-proliferative activity, active members further evaluated for their inhibitory polymerisation. Compounds 21 32 highest effect 9.11 10.5 nM, respectively. Such showed higher than that 10.6 nM) CA-4 13.2 nM). impact compound 25 on cycle distribution was assessed. results revealed can arrest at G2/M phase. Annexin V PI double staining assay carried out explore apoptotic compounds. Compound induced HepG-2 thirteen times more control cells. To examine pattern target heterodimers site, molecular docking studies out.

Language: Английский

Citations

63
New quinoxaline-2(1H)-ones as potential VEGFR-2 inhibitors: design, synthesis, molecular docking, ADMET profile and anti-proliferative evaluations DOI
Reda G. Yousef,

Helmy Sakr,

Ibrahim H. Eissa

et al.

New Journal of Chemistry, Journal Year: 2021, Volume and Issue: 45(36), P. 16949 - 16964

Published: Jan. 1, 2021

Eleven new quinoxaline derivatives were designed and synthesized as modified VEGFR-2 inhibitors of our previous work.

Language: Английский

Citations

63
The Assessment of Anticancer and VEGFR-2 Inhibitory Activities of a New 1H-Indole Derivative: In Silico and In Vitro Approaches DOI Open Access
Eslam B. Elkaeed, Reda G. Yousef, Hazem Elkady

et al.

Processes, Journal Year: 2022, Volume and Issue: 10(7), P. 1391 - 1391

Published: July 17, 2022

Corresponding to the reported features of anti-VEGFR-2-approved compounds, a new 1H-indole derivative (compound 7) was designed. The inhibitory potential designed compound revealed via molecular docking study that showed appropriate binding. Then, MD simulation (six studies) over period 100 ns performed confirm precise binding and optimum energy. Additionally, MM-GBSA reaffirmed perfect binding, exhibiting total energy −40.38 Kcal/Mol. experiments named essential amino acids in protein–ligand interaction, employing decomposition revealing diversity interactions 7 inside VEGFR-2 enzyme. As is new, DFT were utilized for structure optimization. results validated coherent interaction with A good value drug-likeness acknowledged silico ADMET studies. Interestingly, experimental vitro prohibitory better than sorafenib, demonstrating an IC50 25 nM. Notably, strong effects 10 against two cancer cell lines (MCF-7 HCT 116) established values 12.93 11.52 μM, disclosing high selectivity indexes 6.7 7.5, respectively.

Language: Английский

Citations

45