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Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity

α-Aminoamidines are promising reagents for the synthesis of a diverse family of pyrimidine ring derivatives. Here, we demonstrate the use of α-aminoamidines for the synthesis of a new series of 5,6,7,8-tetrahydroquinazolines by their reaction with bis-benzylidene cyclohexanones. The reaction occurs...

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Autores principales: Snizhko, Arsenii D., Kyrychenko, Alexander V., Gladkov, Eugene S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999073/
https://www.ncbi.nlm.nih.gov/pubmed/35409144
http://dx.doi.org/10.3390/ijms23073781
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author Snizhko, Arsenii D.
Kyrychenko, Alexander V.
Gladkov, Eugene S.
author_facet Snizhko, Arsenii D.
Kyrychenko, Alexander V.
Gladkov, Eugene S.
author_sort Snizhko, Arsenii D.
collection PubMed
description α-Aminoamidines are promising reagents for the synthesis of a diverse family of pyrimidine ring derivatives. Here, we demonstrate the use of α-aminoamidines for the synthesis of a new series of 5,6,7,8-tetrahydroquinazolines by their reaction with bis-benzylidene cyclohexanones. The reaction occurs in mild conditions and is characterized by excellent yields. It has easy workup, as compared to the existing methods of tetrahydroquinazoline preparation. Newly synthesized derivatives of 5,6,7,8-tetrahydroquinazoline bear protecting groups at the C2-tert-butyl moiety of a quinazoline ring, which can be easily cleaved, opening up further opportunities for their functionalization. Moreover, molecular docking studies indicate that the synthesized compounds reveal high binding affinity toward some essential enzymes of Mycobacterial tuberculosis, such as dihydrofolate reductase (DHFR), pantothenate kinase (MtPanK), and FAD-containing oxidoreductase DprE1 (MtDprE1), so that they may be promising candidates for the molecular design and the development of new antitubercular agents against multidrug-resistant strains of the Tubercle bacillus. Finally, the high inhibition activity of the synthesized compounds was also predicted against β-glucosidase, suggesting a novel tetrahydroquinazoline scaffold for the treatment of diabetes.
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spelling pubmed-89990732022-04-12 Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity Snizhko, Arsenii D. Kyrychenko, Alexander V. Gladkov, Eugene S. Int J Mol Sci Article α-Aminoamidines are promising reagents for the synthesis of a diverse family of pyrimidine ring derivatives. Here, we demonstrate the use of α-aminoamidines for the synthesis of a new series of 5,6,7,8-tetrahydroquinazolines by their reaction with bis-benzylidene cyclohexanones. The reaction occurs in mild conditions and is characterized by excellent yields. It has easy workup, as compared to the existing methods of tetrahydroquinazoline preparation. Newly synthesized derivatives of 5,6,7,8-tetrahydroquinazoline bear protecting groups at the C2-tert-butyl moiety of a quinazoline ring, which can be easily cleaved, opening up further opportunities for their functionalization. Moreover, molecular docking studies indicate that the synthesized compounds reveal high binding affinity toward some essential enzymes of Mycobacterial tuberculosis, such as dihydrofolate reductase (DHFR), pantothenate kinase (MtPanK), and FAD-containing oxidoreductase DprE1 (MtDprE1), so that they may be promising candidates for the molecular design and the development of new antitubercular agents against multidrug-resistant strains of the Tubercle bacillus. Finally, the high inhibition activity of the synthesized compounds was also predicted against β-glucosidase, suggesting a novel tetrahydroquinazoline scaffold for the treatment of diabetes. MDPI 2022-03-29 /pmc/articles/PMC8999073/ /pubmed/35409144 http://dx.doi.org/10.3390/ijms23073781 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Snizhko, Arsenii D.
Kyrychenko, Alexander V.
Gladkov, Eugene S.
Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity
title Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity
title_full Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity
title_fullStr Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity
title_full_unstemmed Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity
title_short Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity
title_sort synthesis of novel derivatives of 5,6,7,8-tetrahydroquinazolines using α-aminoamidines and in silico screening of their biological activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999073/
https://www.ncbi.nlm.nih.gov/pubmed/35409144
http://dx.doi.org/10.3390/ijms23073781
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