Novel sulfonamide-tethered Schiff bases as anti-proliferative agents with VEGFR-2 inhibitory activity: Synthesis, biological assessment, and molecular dynamic simulations

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1309, P. 138148 - 138148

Published: March 26, 2024

Language: Английский

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Dual VEGFR-2 and EGFR ^T790M inhibitors of phenyldiazenes: anticancer evaluations, ADMET, docking, design and synthesis

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 17(3), P. 287 - 300

Published: Jan. 17, 2025

New phenyldiazene scaffold-linked heterocyclic pyrazole, pyrimidinone, pyrimidinthione, and/or triazine rings have been developed and synthesized. Cytotoxicity of our derivatives was estimated on four cancer VERO normal cell lines targeting EGFRT790M (epidermal growth factor receptor) VEGFR-2 (vascular endothelial receptor-2) enzymes. Our new selectively inhibited both EGFR as they the essential structural requirements for inhibitors receptors. Derivative 14 most active A549, HCT116, HepG2, MCF-7 cancers with half-maximal inhibitory concentration (IC50) = 5.50, 9.77, 7.12, 7.85 µM respectively. The assessed 5, 7, 8, 9, 10, 12 showed IC50 54.40-62.60 μM against (normal kidney) cells low toxicity. In addition, 14, 7 9 were discovered to be very good at values 1.15, 1.35, 140, 1.78 1.90 µM, Furthermore, strongly repressed 0.28, 0.33, 0.35, 0.50 correspondingly. Additionally, highly compounds ADMET profile. could considered anticancer agents dual inhibition.

Language: Английский

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In Silico Exploration of Potential Natural Inhibitors against SARS-Cov-2 nsp10

Molecules, Journal Year: 2021, Volume and Issue: 26(20), P. 6151 - 6151

Published: Oct. 12, 2021

In continuation of our previous effort, different in silico selection methods were applied to 310 naturally isolated metabolites that exhibited antiviral potentialities before. The aimed pick the most relevant inhibitor SARS-CoV-2 nsp10. At first, a structural similarity study against co-crystallized ligand, S-Adenosyl Methionine (SAM), nonstructural protein (nsp10) (PDB ID: 6W4H) was carried out. analysis culled 30 candidates. Secondly, fingerprint SAM preferred compounds 44, 48, 85, 102, 105, 182, 220, 221, 282, 284, 285, 301, and 302. docking studies picked 284. While ADMET expected likeness five candidates be drugs, toxicity 48 182. Finally, density-functional theory (DFT) suggested vidarabine (182) SARS-Cov-2 nsp10 inhibitor.

Language: Английский

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Phthalazine‐based VEGFR‐2 inhibitors: Rationale, design, synthesis, in silico, ADMET profile, docking, and anticancer evaluations

Archiv der Pharmazie, Journal Year: 2021, Volume and Issue: 354(11)

Published: Aug. 19, 2021

In the designed compounds, a new linker was inserted in form of fragments with verified VEGFR-2 inhibitory potential, including an α,β-unsaturated ketonic fragment, pyrazole, and pyrimidine. Also, distal hydrophobic moieties were attached to these linkers that are expected increase interaction and, consequently, affinity. These structural optimizations have led us identify novel dihydropyrazole derivative 6e as promising hit molecule. All derivatives evaluated assess their anticancer activity against three human cancer cell lines, HepG2, HCT-116, MCF-7. The results vitro evaluation study revealed moderate excellent cytotoxicity 6c , 6g 7b IC50 values low micromolar range. investigated for 16 compounds. enzyme assay compounds compared those sorafenib reference inhibitor. obtained demonstrated our potent inhibitors. most showed range 0.11-0.22 µM. Molecular docking pharmacokinetic studies also conducted rationalize evaluate ability be developed good drug candidates.

Language: Английский

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

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

Published: Dec. 18, 2021

Language: Английский

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