New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors

New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors Publisher Pubmed

Naimi N¹ ; Karimian S² ; Dastyafteh N¹ ; Noori M¹ ; Mohammadikhanaposhtani M³ ; Dadgar A⁴ ; Larijani B¹ ; Lotfi V¹ ; Celik I⁵ ; Aktas A⁶ ; Sadeghian N⁷ ; Taslimi P⁷ ; Mahdavi M¹

Show Affiliations

1. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
2. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
4. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
5. Department of Chemistry, Faculty of Science, Eskisehir Technical University, Eskisehir, Turkey
6. Vocational School of Health Service, Inonu University, Malatya, Turkey
7. Department of Biotechnology, Faculty of Science, Bartin University, Bartin, Turkey

Source: Archiv der Pharmazie Published:2025

Abstract

New derivatives 6a–m with benzimidazole–indole–amide scaffold were developed, synthesized, and assessed for potential inhibitory effects on α-glucosidase and acetylcholinesterase (AChE). These compounds were synthesized by various amine derivatives. With the exception of two compounds, the α-glucosidase inhibitory activities of the title derivatives were more than that of the positive control acarbose. Moreover, the anti-AChE activity of these compounds, with the exception of one compound, was better than that of tacrine (standard inhibitor). The most potent compound against α-glucosidase was 3-methylphenyl derivative 6i and the most potent compound against AChE was 3,4-dimethoxyphenethyl derivative 6m. All the synthesized compounds were placed in the active sites of α-glucosidase and AChE by in silico docking method and the obtained binding energies were approximately in agreement with the in vitro observed data. Interaction modes of the most potent compounds 6i and 6m demonstrated that these compounds interacted with important residues of their target enzymes. Molecular dynamics simulation was conducted specifically on compound 6i in complex with α-glucosidase to obtain deeper insights into the behavior of this molecule. Furthermore, in silico pharmacokinetic and toxicity studies on the most potent compound predicted that these compounds have good profiles in terms of oral absorption and toxicity. © 2024 Deutsche Pharmazeutische Gesellschaft.

Style	Citing Format
MLA	Naimi N, et al.. "New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors." Archiv der Pharmazie, vol. 358, no. 1, 2025, pp. -.
APA	Naimi N, Karimian S, Dastyafteh N, Noori M, Mohammadikhanaposhtani M, Dadgar A, Larijani B, Lotfi V, Celik I, Aktas A, Sadeghian N, Taslimi P, Mahdavi M (2025). New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors. Archiv der Pharmazie, 358(1), -.
Chicago	Naimi N, Karimian S, Dastyafteh N, Noori M, Mohammadikhanaposhtani M, Dadgar A, Larijani B, et al.. "New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors." Archiv der Pharmazie 358, no. 1 (2025): -.
Harvard	Naimi N et al. (2025) 'New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors', Archiv der Pharmazie, 358(1), pp. -.
Vancouver	Naimi N, Karimian S, Dastyafteh N, Noori M, Mohammadikhanaposhtani M, Dadgar A, et al.. New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors. Archiv der Pharmazie. 2025;358(1):-.
BibTex	@article{ author = {Naimi N and Karimian S and Dastyafteh N and Noori M and Mohammadikhanaposhtani M and Dadgar A and Larijani B and Lotfi V and Celik I and Aktas A and Sadeghian N and Taslimi P and Mahdavi M}, title = {New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors}, journal = {Archiv der Pharmazie}, volume = {358}, number = {1}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Naimi N AU - Karimian S AU - Dastyafteh N AU - Noori M AU - Mohammadikhanaposhtani M AU - Dadgar A AU - Larijani B AU - Lotfi V AU - Celik I AU - Aktas A AU - Sadeghian N AU - Taslimi P AU - Mahdavi M TI - New Benzimidazole–Indole–Amide Derivatives As Potent Α-Glucosidase and Acetylcholinesterase Inhibitors JO - Archiv der Pharmazie VL - 358 IS - 1 SP - EP - PY - 2025 ER -

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