Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes

Muhammad Yar; Marek Bajda; Sohail Shahzad; Nisar Ullah; Mazhar Amjad Gilani; Muhammad Ashraf; Abdul Rauf; Ayesha Shaukat

doi:10.1016/j.bioorg.2014.11.006

Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes

Muhammad Yar^*, Marek Bajda, Sohail Shahzad, Nisar Ullah, Mazhar Amjad Gilani, Muhammad Ashraf, Abdul Rauf, Ayesha Shaukat

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

A new and efficient solvent free synthesis of 2,4,5-trisubstituted imidazoles (3a-3j) was achieved by N-acetyl glycine (NAG) catalyzed three components condensation of aldehydes, benzil and ammonium acetate. Our synthetic methodology accommodated a range of various substituted alkyl and aryl aldehydes. Evaluation of α-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good α-glucosidase inhibition at low micro-molar concentrations. Among the synthesized compounds, compound 3c, bearing the ortho-hydroxy phenyl substituent at position 2 displayed the highest inhibitory activity with an IC₅₀ value 74.32 ± 0.59 μM. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed.

Original language	English
Pages (from-to)	65-71
Number of pages	7
Journal	Bioorganic Chemistry
Volume	58
DOIs	https://doi.org/10.1016/j.bioorg.2014.11.006
State	Published - Feb 2015

Bibliographical note

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© 2014 Elsevier B.V. All rights reserved.

Keywords

Baker's yeast
Diabetes
Imidazoles
Molecular modeling
Organocatalysis
α-glucosidase inhibition

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bioorg.2014.11.006

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title = "Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes",

abstract = "A new and efficient solvent free synthesis of 2,4,5-trisubstituted imidazoles (3a-3j) was achieved by N-acetyl glycine (NAG) catalyzed three components condensation of aldehydes, benzil and ammonium acetate. Our synthetic methodology accommodated a range of various substituted alkyl and aryl aldehydes. Evaluation of α-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good α-glucosidase inhibition at low micro-molar concentrations. Among the synthesized compounds, compound 3c, bearing the ortho-hydroxy phenyl substituent at position 2 displayed the highest inhibitory activity with an IC50 value 74.32 ± 0.59 μM. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed.",

keywords = "Baker's yeast, Diabetes, Imidazoles, Molecular modeling, Organocatalysis, α-glucosidase inhibition",

author = "Muhammad Yar and Marek Bajda and Sohail Shahzad and Nisar Ullah and Gilani, \{Mazhar Amjad\} and Muhammad Ashraf and Abdul Rauf and Ayesha Shaukat",

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doi = "10.1016/j.bioorg.2014.11.006",

language = "English",

volume = "58",

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journal = "Bioorganic Chemistry",

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T1 - Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes

AU - Yar, Muhammad

AU - Bajda, Marek

AU - Shahzad, Sohail

AU - Ullah, Nisar

AU - Gilani, Mazhar Amjad

AU - Ashraf, Muhammad

AU - Rauf, Abdul

AU - Shaukat, Ayesha

PY - 2015/2

Y1 - 2015/2

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AB - A new and efficient solvent free synthesis of 2,4,5-trisubstituted imidazoles (3a-3j) was achieved by N-acetyl glycine (NAG) catalyzed three components condensation of aldehydes, benzil and ammonium acetate. Our synthetic methodology accommodated a range of various substituted alkyl and aryl aldehydes. Evaluation of α-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good α-glucosidase inhibition at low micro-molar concentrations. Among the synthesized compounds, compound 3c, bearing the ortho-hydroxy phenyl substituent at position 2 displayed the highest inhibitory activity with an IC50 value 74.32 ± 0.59 μM. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed.

KW - Baker's yeast

KW - Diabetes

KW - Imidazoles

KW - Molecular modeling

KW - Organocatalysis

KW - α-glucosidase inhibition

UR - https://www.scopus.com/pages/publications/84914674502

U2 - 10.1016/j.bioorg.2014.11.006

DO - 10.1016/j.bioorg.2014.11.006

M3 - Article

C2 - 25462626

AN - SCOPUS:84914674502

SN - 0045-2068

VL - 58

SP - 65

EP - 71

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

ER -

Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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