Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study

Abstract Many pyridopyrimidine moieties linked to the coumarin ring were synthesized by the reaction of malononitrile with 7-hydroxy-4-methyl-2-oxo-2 H-chromene-8-carbaldehyde (2) directly in the presence of ammonium acetate and different ketones and studied the effect of other basic catalysis, rati...

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Main Authors: Nehal A. E. Youssef, Yasser A. Selim, Lina A. Shaheen, Ahmed A. Fadda, Hatem E. Gaffer, Sherihan A. El-Hadidy
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05325-1
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author Nehal A. E. Youssef
Yasser A. Selim
Lina A. Shaheen
Ahmed A. Fadda
Hatem E. Gaffer
Sherihan A. El-Hadidy
author_facet Nehal A. E. Youssef
Yasser A. Selim
Lina A. Shaheen
Ahmed A. Fadda
Hatem E. Gaffer
Sherihan A. El-Hadidy
author_sort Nehal A. E. Youssef
collection DOAJ
description Abstract Many pyridopyrimidine moieties linked to the coumarin ring were synthesized by the reaction of malononitrile with 7-hydroxy-4-methyl-2-oxo-2 H-chromene-8-carbaldehyde (2) directly in the presence of ammonium acetate and different ketones and studied the effect of other basic catalysis, ratio of reactants and the effect of the solvent. The newly synthesized compounds were evaluated for their cytotoxic activity against four cell lines namely HepG2, WI-38, VERO, and MCF-7. The cytotoxic activity showed that compounds 8, 9, 10, and 7 have the highest activity against the studied cell lines. Focusing on the binding affinity and interactions between the five synthesized derivatives with the highest anticancer activity and specific amino acids of 4HJO residues over the molecular docking analysis. Derivative 10 recorded the highest energy score with good RMSD compared to the rest of the derivatives.
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spelling doaj-art-966bfe391976490fa1a5261b45db80c02025-08-20T03:22:49ZengNature PortfolioScientific Reports2045-23222025-06-0115111410.1038/s41598-025-05325-1Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking studyNehal A. E. Youssef0Yasser A. Selim1Lina A. Shaheen2Ahmed A. Fadda3Hatem E. Gaffer4Sherihan A. El-Hadidy5Department of Chemistry, Faculty of Science, Mansoura UniversityFaculty of Specific Education, Zagazig UniversityFaculty of Pharmacy, The British University in EgyptDepartment of Chemistry, Faculty of Science, Mansoura UniversityDepartment of Dyeing, Printing, and Auxiliaries, Textile InstituteDepartment of Engineering Chemistry, Canal High Institute of Engineering and TechnologyAbstract Many pyridopyrimidine moieties linked to the coumarin ring were synthesized by the reaction of malononitrile with 7-hydroxy-4-methyl-2-oxo-2 H-chromene-8-carbaldehyde (2) directly in the presence of ammonium acetate and different ketones and studied the effect of other basic catalysis, ratio of reactants and the effect of the solvent. The newly synthesized compounds were evaluated for their cytotoxic activity against four cell lines namely HepG2, WI-38, VERO, and MCF-7. The cytotoxic activity showed that compounds 8, 9, 10, and 7 have the highest activity against the studied cell lines. Focusing on the binding affinity and interactions between the five synthesized derivatives with the highest anticancer activity and specific amino acids of 4HJO residues over the molecular docking analysis. Derivative 10 recorded the highest energy score with good RMSD compared to the rest of the derivatives.https://doi.org/10.1038/s41598-025-05325-1Cyclic ketoneCoumarinPyridopyrimidineCytotoxicityMolecular Docking
spellingShingle Nehal A. E. Youssef
Yasser A. Selim
Lina A. Shaheen
Ahmed A. Fadda
Hatem E. Gaffer
Sherihan A. El-Hadidy
Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study
Scientific Reports
Cyclic ketone
Coumarin
Pyridopyrimidine
Cytotoxicity
Molecular Docking
title Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study
title_full Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study
title_fullStr Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study
title_full_unstemmed Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study
title_short Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study
title_sort design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study
topic Cyclic ketone
Coumarin
Pyridopyrimidine
Cytotoxicity
Molecular Docking
url https://doi.org/10.1038/s41598-025-05325-1
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