New quinazoline sulfonamide derivatives as potential anticancer agents: Identifying a promising hit with dual EGFR/VEGFR-2 inhibitory and radiosensitizing activity

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 140, P. 106791 - 106791

Published: Aug. 15, 2023

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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Five and six membered heterocyclic rings endowed with azobenzene as dual EGFR^T790M and VEGFR-2 inhibitors: design, synthesis, in silico ADMET profile, molecular docking, dynamic simulation and anticancer evaluations

RSC Advances, Journal Year: 2023, Volume and Issue: 13(50), P. 35321 - 35338

Published: Jan. 1, 2023

Novel azobenzene scaffold-joined heterocyclic isoxazole, pyrazole, triazole, and/or triazine moieties have been developed and synthesized utilizing microwave traditional methods. Our compounds were tested for growth inhibition of A549, MCF-7, HCT-116, HepG2 tumors by dual targeting the VEGFR-2 EGFRT790M enzymes. The suggested compound's manner binding with active sites was explored through molecular design MD modeling. information from results biological screening docking studies highly correlated. A549 cell line one that responded to novel effects most effectively. Having IC50 values 5.15, 6.37, 8.44 6.23 μM, respectively, 14 effective derivative on four HCT116 cancer cells. It had greater activity than erlotinib slightly inferior activities lines sorafenib, respectively. cytotoxicity derivatives, 5, 6, 10 14, evaluated against typical VERO lines. ranging 42.32 55.20 showed investigated drugs modest toxicity normal Additionally all derivatives assessed their inhibitory effects. Among them, 5 established as greatest inhibitors at 0.95, 1.25 1.50 μM correspondingly. As well, could inhibit demonstrating strongest = 0.25, 0.35, 0.40 0.50 Furthermore, ADMET profile in contrast reference sorafenib erlotinib.

Language: Английский

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Pyrazolo[3,4-d]pyrimidine derivatives as EGFRT790M and VEGFR-2 dual TK inhibitors: Design, synthesis, molecular docking, ADMET profile and anticancer evaluations

Journal of Molecular Structure, Journal Year: 2023, Volume and Issue: 1291, P. 136047 - 136047

Published: June 20, 2023

Language: Английский

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Anticancer evaluations of iodoquinazoline substituted with allyl and/or benzyl as dual inhibitors of EGFR^WT and EGFR^T790M: design, synthesis, ADMET and molecular docking

RSC Advances, Journal Year: 2024, Volume and Issue: 14(12), P. 7964 - 7980

Published: Jan. 1, 2024

Fifteen new iodoquinazoline derivatives, 5a,b to 18, are reported in this study and their anticancer evaluation as dual inhibitors of EGFR WT T790M .

Language: Английский

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Exploration of the VEGFR-2 inhibition activity of phthalazine derivatives: design, synthesis, cytotoxicity, ADMET, molecular docking and dynamic simulation

RSC Advances, Journal Year: 2024, Volume and Issue: 14(30), P. 21668 - 21681

Published: Jan. 1, 2024

Novel phthalazine derivatives were designed, synthesized and evaluated against Hep G2 MCF-7 as VEGFR-2 inhibitors.

Language: Английский

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Synthesis, in vitro analysis and molecular docking study of novel benzoxazole-based oxazole derivatives for the treatment of Alzheimer’s disease

Arabian Journal of Chemistry, Journal Year: 2023, Volume and Issue: 16(11), P. 105244 - 105244

Published: Sept. 6, 2023

Alzheimer's disease (AD) is treated by targeting cholinesterase enzymes like acetylcholinesterase and butyrylcholinesterase, these enzymes' inhibitors serve as important tools for treatment of alzheimer diseases. Hybrid analogues with a 1,3-oxazole moiety based on benzoxazole were designed, developed, then tested their inhibition. All the newly synthesized showed moderate to good inhibitory potentials having IC50 values raging between 0.90 ± 0.05µM 35.20 0.70 µM against 1.10 0.10µM 37.70 0.60µM butyrylcholinesterase enzymes. Among series, analogue 11 (IC50 = 0.05µM), 0.10µM) 18 1.20 2.10 being strongest compared standard donepezil drug. Nonetheless, remaining also displayed better inhibition profile both targeted Furthermore, structures all confirmed using HREI-MS, 1HNMR 13CNMR spectroscopy. Additionally, molecular docking experiments conducted determine potential mode interaction majority active enzyme site. The findings corroborated experimental data.

Language: Английский

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Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12416 - 12416

Published: Aug. 4, 2023

Sixteen new thalidomide analogs were synthesized. The candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate (PC3), and breast (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, XIVc IC50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher than all tested lines. Compound XIIIa the most candidate, with an of ± 0.11, 2.51 0.2, 0.82 0.02 µg/mL compared 11.26 0.54, 14.58 0.57, 16.87 0.7 for HepG-2, PC3, MCF-7 cells, respectively. Furthermore, compound reduced expression NFκB P65 levels HepG-2 cells 278.1 pg/mL 63.1 110.5 thalidomide. Moreover, induced eightfold increase caspase-8 a simultaneous decrease TNF-α VEGF cells. Additionally, apoptosis cycle arrest. Our results reveal are potential anticancer candidates, particularly XIVc. Consequently, they should be considered further evaluation development drugs.

Language: Английский

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Iodoquinazoline-derived VEGFR-2 and EGFRT790M dual inhibitors: Design, synthesis, molecular docking and anticancer evaluations

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 143, P. 107062 - 107062

Published: Dec. 25, 2023

Language: Английский

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The Benzoxazole Heterocycle: A Comprehensive Review of the Most Recent Medicinal Chemistry Developments of Antiproliferative, Brain-Penetrant, and Anti-inflammatory Agents

Topics in Current Chemistry, Journal Year: 2024, Volume and Issue: 382(4)

Published: Oct. 21, 2024

Language: Английский

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