VEGFER-2 INHIBITORS AND QUINAZOLINE-BASED ANTICANCER AGENTS DOI Creative Commons

Helmy Sakr,

Islam Otify,

Rezk R. Ayyad

et al.

˜Al-œAzhar Journal of Pharmaceutical Sciences/Al-Azhar Journal of Pharmaceutical Sciences, Journal Year: 2023, Volume and Issue: 68(2), P. 111 - 129

Published: Sept. 1, 2023

Inhibitors of vascular endothelial growth factor receptor -2 (VEGFR-2) are crucial biological targets for the development novel anticancer medications. Quinazoline also plays an important role as one building elements numerous drugs. Thus, a review literature on VEGFR-2 inhibitors and Quinazoline-based medicines has been completed. We introduced now undergoing clinical evaluation, such Gefitinib, Erlotinib, Vandetanib, Afatinib, Lenvatinib, Cabozantinib, Sorafenib Regorafenib in our survey. Additionally, that under were introduced.

Language: Английский

Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies DOI

Reda R. Mabrouk,

Hazem A. Mahdy,

Abdallah E. Abdallah

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: Feb. 25, 2025

New triazoloquinazoline derivatives were synthesized to explore their cytotoxic activity on various cancer cell lines, prompted by the need for effective anticancer agents. All compounds confirmed spectroscopic methods and tested in vitro inhibitory activities against hepatocellular carcinoma (HepG-2), breast (MCF-7), prostate (PC3) lines. Ten VEGFR-2. Additionally, studies investigated most active compound 6, including cycle analysis, apoptotic assessment, effect gene expression, safety profiling, molecular docking, MD simulation, ADMET analysis. Compounds 3a, 3c, 6 exhibited higher MCF-7 than doxorubicin. Compound was potent, arresting at G1 phase showing proapoptotic action. It significantly inhibited VEGFR-2 altered promoting BAX, P21, P53 while downregulating BCL-2. Docking simulations indicated stable interaction with VEGFR-2, safety, profiles suggested favorable drug-likeness safety. has shown promising potential, particularly cancer, but further research is needed confirm these findings address long-term

Language: Английский

Citations

0
Spiroindoline quinazolinedione derivatives as inhibitors of P-glycoprotein: potential agents for overcoming multidrug resistance in cancer therapy DOI
Fatemeh Moosavi,

Masoumeh Divar,

Soghra Khabnadideh

et al.

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

Citations

0
Chemistry, Synthesis, and Structure Activity Relationship of Anticancer Quinoxalines DOI Creative Commons
Mohamed F. Zayed

Chemistry, Journal Year: 2023, Volume and Issue: 5(4), P. 2566 - 2587

Published: Nov. 14, 2023

Quinoxaline is a fused heterocycle system of benzene ring and pyrazine ring. It has earned considerable attention due to its importance in the field medicinal chemistry. The extensive comprehensive array biological activities. derivatives have been used as anticancer, anticonvulsant, anti-inflammatory, antidiabetic, antioxidant, antibacterial, anti-TB, antimalarial, antiviral, anti-HIV, many other uses. Variously substituted quinoxalines are significant therapeutic agents pharmaceutical industry. This review spotlights on chemistry, physiochemical characters, synthesis, products, chemistry various anticancer quinoxaline that were developed last period. covers period from 2016 2023.

Language: Английский

Citations

8
New vatalanib analogs: design, synthesis, in silico study and biological evaluation for anticancer activity DOI
Abdallah E. Abdallah, Hazem Elkady, Alaa Elwan

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1322, P. 140595 - 140595

Published: Nov. 3, 2024

Language: Английский

Citations

2
Design, Synthesis, and Biological Evaluation of Novel Quinazoline Derivatives Possessing a Trifluoromethyl Moiety as Potential Antitumor Agents DOI

M Chen,

Sha Cheng,

Xing Dai

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(5)

Published: April 11, 2024

Abstract A novel series of trifluoromethyl‐containing quinazoline derivatives with a variety functional groups was designed, synthesized, and tested for their antitumor activity by following pharmacophore hybridization strategy. Most the 20 compounds displayed moderate to excellent antiproliferative against five different cell lines (PC3, LNCaP, K562, HeLa, A549). After three rounds screening structural optimization, compound 10 b identified as most potent one, IC 50 values 3.02, 3.45, 3.98 μM PC3, K562 cells, respectively, which were comparable effect positive control gefitinib. To further explore mechanism action cancer, experiments focusing on apoptosis induction, cycle arrest, migration assay conducted. The results showed that able induce prevent tumor migration, but had no cells.

Language: Английский

Citations

1
Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers DOI
Reda G. Yousef, Ibrahim H. Eissa, Hazem Elkady

et al.

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(24), P. 2583 - 2598

Published: Nov. 14, 2024

Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.

Language: Английский

Citations

1
Novel Aminopyrimidine-2,4-diones, 2-Thiopyrimidine-4-ones, and 6-Arylpteridines as Dual-Target Inhibitors of BRD4/PLK1: Design, Synthesis, Cytotoxicity, and Computational Studies DOI Creative Commons
Samar El‐Kalyoubi, Samiha A. El‐Sebaey, Sherin M. Elfeky

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(9), P. 1303 - 1303

Published: Sept. 15, 2023

Structural-based drug design and solvent-free synthesis were combined to obtain three novel series of 5-arylethylidene-aminopyrimidine-2,4-diones (4, 5a-c, 6a,b), 5-arylethylidene-amino-2-thiopyrimidine-4-ones (7,8), 6-arylpteridines (9,10) as dual BRD4 PLK1 inhibitors. MTT assays synthesized compounds against breast (MDA-MB-231), colorectal (HT-29), renal (U-937) cancer cells showed excellent-to-good cytotoxic activity, compared Methotrexate; MDA-MB-231 the most sensitive cells. The active tested normal Vero Compounds 4 7 significantly inhibited PLK1, with IC50 values 0.029, 0.042 µM, 0.094, 0.02 respectively, which are nearly comparable volasertib (IC50 = 0.017 0.025 µM). Compound triggered apoptosis halted cell growth at G2/M phase, similarly volasertib. It also upregulated BAX caspase-3 markers while downregulating Bcl-2 gene. Finally, fitted binding site ideal drug-like properties pharmacokinetics, making them promising anticancer candidates.

Language: Английский

Citations

3
DUAL INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) AND TRYPTOPHAN-2,3-DIOXYGENASE (TDO) AS ANTI-TUMOR IMMUNE MODULATORS DOI Creative Commons
Mohamed Ayman El‐Zahabi,

Mostafa Youssef Abouzeid,

Ibrahim H. Eissa

et al.

˜Al-œAzhar Journal of Pharmaceutical Sciences/Al-Azhar Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: 69(1), P. 38 - 61

Published: March 1, 2024

Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are enzymes that catalyze the rate-limiting step of kynurenine pathway. Recent literature reports IDO TDO upregulation in tumor cells leading to L-tryptophan depletion accumulation tryptophan metabolites. This process represents an essential mechanism for tumor-induced immunosuppression. Following failure Epacadostat, inhibitor, phase 3 clinical trials, numerous studies have shifted a dual inhibition scheme overcome compensation linked TDO. Therefore, using single molecule emerges as highly promising therapeutic approach. comprehensive review aims discuss successful scaffolds reported inhibitors their inhibitory values against both enzymes. The active compounds potential form novel chemical class anti-tumor immune modulator drugs.

Language: Английский

Citations

0
VEGFER-2 INHIBITORS AND QUINAZOLINE-BASED ANTICANCER AGENTS DOI Creative Commons

Helmy Sakr,

Islam Otify,

Rezk R. Ayyad

et al.

˜Al-œAzhar Journal of Pharmaceutical Sciences/Al-Azhar Journal of Pharmaceutical Sciences, Journal Year: 2023, Volume and Issue: 68(2), P. 111 - 129

Published: Sept. 1, 2023

Inhibitors of vascular endothelial growth factor receptor -2 (VEGFR-2) are crucial biological targets for the development novel anticancer medications. Quinazoline also plays an important role as one building elements numerous drugs. Thus, a review literature on VEGFR-2 inhibitors and Quinazoline-based medicines has been completed. We introduced now undergoing clinical evaluation, such Gefitinib, Erlotinib, Vandetanib, Afatinib, Lenvatinib, Cabozantinib, Sorafenib Regorafenib in our survey. Additionally, that under were introduced.

Language: Английский

Citations

1