Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

Abstract In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient,...

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Autores principales:	Fariba Peytam, Ghazaleh Takalloobanafshi, Toktam Saadattalab, Maryam Norouzbahari, Zahra Emamgholipour, Setareh Moghimi, Loghman Firoozpour, Hamid Reza Bijanzadeh, Mohammad Ali Faramarzi, Somayeh Mojtabavi, Parviz Rashidi-Ranjbar, Saeed Karima, Roya Pakraad, Alireza Foroumadi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/456f94aaf8724f58b9eb5aa1e234c49f
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spelling	oai:doaj.org-article:456f94aaf8724f58b9eb5aa1e234c49f2021-12-02T17:30:40ZDesign, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase10.1038/s41598-021-91473-z2045-2322https://doaj.org/article/456f94aaf8724f58b9eb5aa1e234c49f2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91473-zhttps://doaj.org/toc/2045-2322Abstract In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.Fariba PeytamGhazaleh TakalloobanafshiToktam SaadattalabMaryam NorouzbahariZahra EmamgholipourSetareh MoghimiLoghman FiroozpourHamid Reza BijanzadehMohammad Ali FaramarziSomayeh MojtabaviParviz Rashidi-RanjbarSaeed KarimaRoya PakraadAlireza ForoumadiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fariba Peytam Ghazaleh Takalloobanafshi Toktam Saadattalab Maryam Norouzbahari Zahra Emamgholipour Setareh Moghimi Loghman Firoozpour Hamid Reza Bijanzadeh Mohammad Ali Faramarzi Somayeh Mojtabavi Parviz Rashidi-Ranjbar Saeed Karima Roya Pakraad Alireza Foroumadi Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase
description	Abstract In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.
format	article
author	Fariba Peytam Ghazaleh Takalloobanafshi Toktam Saadattalab Maryam Norouzbahari Zahra Emamgholipour Setareh Moghimi Loghman Firoozpour Hamid Reza Bijanzadeh Mohammad Ali Faramarzi Somayeh Mojtabavi Parviz Rashidi-Ranjbar Saeed Karima Roya Pakraad Alireza Foroumadi
author_facet	Fariba Peytam Ghazaleh Takalloobanafshi Toktam Saadattalab Maryam Norouzbahari Zahra Emamgholipour Setareh Moghimi Loghman Firoozpour Hamid Reza Bijanzadeh Mohammad Ali Faramarzi Somayeh Mojtabavi Parviz Rashidi-Ranjbar Saeed Karima Roya Pakraad Alireza Foroumadi
author_sort	Fariba Peytam
title	Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase
title_short	Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase
title_full	Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase
title_fullStr	Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase
title_full_unstemmed	Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase
title_sort	design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/456f94aaf8724f58b9eb5aa1e234c49f
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Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

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