Quinazoline-based VEGFR-2 inhibitors as potential anti-angiogenic agents: A contemporary perspective of SAR and molecular docking studies

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 259, P. 115626 - 115626

Published: July 8, 2023

Language: Английский

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Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13317 - 13317

Published: Aug. 28, 2023

Vascular endothelial growth factors (VEGFs) are the key regulators of vasculogenesis in normal and oncological development. VEGF-A is most studied angiogenic factor secreted by malignant tumor cells under hypoxic inflammatory stress, which made a rational target for anticancer therapy. However, inhibition monoclonal antibody drugs led to upregulation VEGF-D. VEGF-D was primarily described as lymphangiogenic factor; however, VEGF-D's blood potential comparable has already been demonstrated glioblastoma colorectal carcinoma. These findings suggested role facilitating bypassing anti-VEGF-A antiangiogenic Owing its high mitogenic ability, higher affinity VEGFR-2, expression cancer, might even be stronger driver and, hence, better therapeutic than VEGF-A. In this review, we summarized targetability an therapy cancer.

Language: Английский

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Recent development of VEGFR small molecule inhibitors as anticancer agents: A patent review (2021–2023)

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 146, P. 107278 - 107278

Published: March 9, 2024

Language: Английский

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Novel quinazolin-2-yl 1,2,3-triazole hybrids as promising multi-target anticancer agents: Design, synthesis, and molecular docking study

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 148, P. 107437 - 107437

Published: May 10, 2024

Language: Английский

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Design, synthesis, and apoptotic antiproliferative action of new 1,2,3-triazole/1,2,4-oxadiazole hybrids as dual EGFR/VEGFR-2 inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 39(1)

Published: Feb. 7, 2024

A novel series of 1,2,3-triazole/1,2,4-oxadiazole hybrids (7a–o) was developed as dual inhibitors EGFR/VEGFR-2. Compounds 7a–o were evaluated antiproliferative agents with Erlotinib the reference drug. Results demonstrated that most tested compounds showed significant action GI50 values ranging from 28 to 104 nM, compared (GI50 = 33 nM), and 7i–m potent. 7h, 7i, 7j, 7k, 7l EGFR/VEGFR-2 inhibitors. These in vitro experiments are potent may operate for their apoptotic potential activity, where findings indicated promote apoptosis by activating caspase-3, 8, Bax down-regulating anti-apoptotic Bcl-2. Molecular docking simulations show binding mode active within EGFR VEGFR-2 sites.

Language: Английский

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Design and Synthesis of New Dihydropyrimidine Derivatives with a Cytotoxic Effect as Dual EGFR/VEGFR-2 Inhibitors

ACS Omega, Journal Year: 2024, Volume and Issue: 9(32), P. 34358 - 34369

Published: Aug. 1, 2024

We developed and synthesized tetrahydropyrimidine derivatives as possible cytotoxic agents to inhibit EGFR VEGFR-2 in the present study. Our study completely assesses efficiency of pyrimidine-based

Language: Английский

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Recent Advances and Future Directions on Small Molecule VEGFR Inhibitors in Oncological Conditions

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 272, P. 116472 - 116472

Published: May 6, 2024

Language: Английский

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Identification of Benzothiazoles Bearing 1,3,4-Thiadiazole as Antiproliferative Hybrids Targeting VEGFR-2 and BRAF Kinase: Design, Synthesis, BIO Evaluation and In Silico Study

Molecules, Journal Year: 2024, Volume and Issue: 29(13), P. 3186 - 3186

Published: July 4, 2024

Cancer remains a leading cause of death worldwide, often resulting from uncontrolled growth in various organs. Protein kinase inhibitors represent an important class targeted cancer therapies. Recently, the kinases BRAF and VEGFR-2 have shown synergistic effects on tumor progression. Seeking to develop dual BRAF/VEGFR-2 inhibitors, we synthesized 18 amino-benzothiazole derivatives with structural similarities reported inhibitors. Four compounds-

Language: Английский

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A review of progress in o-aminobenzamide-based HDAC inhibitors with dual targeting capabilities for cancer therapy

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 259, P. 115673 - 115673

Published: July 20, 2023

Language: Английский

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Novel 3-phenylquinazolin-2,4(1H,3H)-diones as dual VEGFR-2/c-Met-TK inhibitors: design, synthesis, and biological evaluation

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 30, 2023

Abstract Multitarget anticancer drugs are more superior than single target regarding patient compliance, drug adverse effects, drug-drug interactions, resistance as well pharmaceutical industry economics. Dysregulation of both VEGFR-2 and c-Met tyrosine kinases (TKs) could result in development progression different human cancers. Herein, we reported a novel series 3-phenylquinazolin-2,4(1 H ,3 )-diones with thiourea moiety dual VEGFR-2/c-Met TKs. Compared to sorafenib, cabozantinib went behind inhibition TK. The inhibitory activity is due longer HB domain that sorafenib. Based on pharmacophore analogues, designed new We synthesized the compounds via pot three-component reaction. cytotoxic was conducted against HCT-116 colorectal cancer cell line. Compounds 3c 3e exhibited highest line (IC 50 1.184 3.403 µM, respectively). vitro enzyme carried out Compound has = 83 48 nM, Docking studies showed α-oxo quinazoline ring formed hydrogen bond Met1160 residue adenine region

Language: Английский

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