Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase

Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase Publisher Pubmed

Yousefnejad F¹ ; Mohammadimoghadamgoozali M² ; Sayahi MH³ ; Halimi M⁴ ; Moazzam A¹ ; Mohammadikhanaposhtani M⁵ ; Mojtabavi S⁶ ; Asadi M⁷ ; Faramarzi MA⁶ ; Larijani B¹ ; Amanlou M² ; Mahdavi M¹

Show Affiliations

1. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
2. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Chemistry, Payame Noor University, P.O. Box 19395-3697, Tehran, Iran
4. Department of Biology, Islamic Azad University, Babol Branch, Babol, Iran
5. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
6. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
7. Department of Medicinal Chemistry, Faculty of Pharmacy, Iran University of Medical Sciences, Tehran, Iran

Source: Scientific Reports Published:2023

Abstract

α-Glucosidase as a carbohydrate-hydrolase enzyme is a crucial therapeutic target for type 2 diabetes. In this work, benzo[d]imidazole-amide containing 1,2,3-triazole-N-arylacetamide derivatives 8a–n were synthesized and evaluated for their inhibitory activity against α-glucosidase. In vitro α-glucosidase inhibition assay demonstrated that more than half of the title compounds with IC50 values in the range of 49.0–668.5 μM were more potent than standard inhibitor acarbose (IC50 = 750.0 µM). The most promising inhibitor was N-2-methylphenylacetamid derivative 8c. Kinetic study revealed that compound 8c (Ki = 40.0 µM) is a competitive inhibitor against α-glucosidase. Significantly, molecular docking and molecular dynamics studies on the most potent compound showed that this compound with a proper binding energy interacted with important amino acids of the α-glucosidase active site. Study on cytotoxicity of the most potent compounds 8c, 8e, and 8g demonstrated that these compounds did not show cytotoxic activity against the cancer and normal cell lines MCF-7 and HDF, respectively. Furthermore, the ADMET study predicted that compound 8c is likely to be orally active and non-cytotoxic. © 2023, The Author(s).

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Style	Citing Format
MLA	Yousefnejad F, et al.. "Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase." Scientific Reports, vol. 13, no. 1, 2023, pp. -.
APA	Yousefnejad F, Mohammadimoghadamgoozali M, Sayahi MH, Halimi M, Moazzam A, Mohammadikhanaposhtani M, Mojtabavi S, Asadi M, Faramarzi MA, Larijani B, Amanlou M, Mahdavi M (2023). Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase. Scientific Reports, 13(1), -.
Chicago	Yousefnejad F, Mohammadimoghadamgoozali M, Sayahi MH, Halimi M, Moazzam A, Mohammadikhanaposhtani M, Mojtabavi S, et al.. "Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase." Scientific Reports 13, no. 1 (2023): -.
Harvard	Yousefnejad F et al. (2023) 'Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase', Scientific Reports, 13(1), pp. -.
Vancouver	Yousefnejad F, Mohammadimoghadamgoozali M, Sayahi MH, Halimi M, Moazzam A, Mohammadikhanaposhtani M, et al.. Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase. Scientific Reports. 2023;13(1):-.
BibTex	@article{ author = {Yousefnejad F and Mohammadimoghadamgoozali M and Sayahi MH and Halimi M and Moazzam A and Mohammadikhanaposhtani M and Mojtabavi S and Asadi M and Faramarzi MA and Larijani B and Amanlou M and Mahdavi M}, title = {Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase}, journal = {Scientific Reports}, volume = {13}, number = {1}, pages = {-}, year = {2023} }
RIS	TY - JOUR AU - Yousefnejad F AU - Mohammadimoghadamgoozali M AU - Sayahi MH AU - Halimi M AU - Moazzam A AU - Mohammadikhanaposhtani M AU - Mojtabavi S AU - Asadi M AU - Faramarzi MA AU - Larijani B AU - Amanlou M AU - Mahdavi M TI - Design, Synthesis, in Vitro, and in Silico Evaluations of Benzo[D]Imidazole-Amide-1,2,3-Triazole-N-Arylacetamide Hybrids As New Antidiabetic Agents Targeting Α-Glucosidase JO - Scientific Reports VL - 13 IS - 1 SP - EP - PY - 2023 ER -

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