Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors

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Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors Publisher

Dastyafteh N ; Ghafouri SN ; Mollazadeh M ; Motamedi Shakib N ; Halimi M ; Hosseini S ; Mojtabavi S ; Faramarzi MA ; Larijani B ; Amanlou M ; Mohammadikhanaposhtani M ; Mahdavi M

Source: RSC Advances Published:2026

Abstract

A series of novel acetamide–indole–benzo[d]imidazole–carboxylic acid hybrids (8a–n) was designed based on the structural scaffolds of known protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitors. Evaluation against PTP1B revealed that six compounds (8d, 8f–h, 8j, and 8l) exhibited superior inhibitory activity compared to the standard inhibitor suramin, while one derivative (8a) demonstrated comparable potency. The remaining compounds showed reduced efficacy relative to suramin. In contrast, only two compounds (8j and 8k) displayed marginally superior α-glucosidase inhibition compared to acarbose, while all other derivatives were less potent than the standard. Based on these results, subsequent investigations focused on the PTP1B inhibitory potential of this series. Kinetic analysis of the most potent compound, 8l, confirmed a competitive inhibition mechanism against PTP1B. Molecular docking studies of the most active compounds yielded binding modes consistent with the in vitro activity, and molecular dynamics simulations further verified the stable binding of compound 8l within the PTP1B active site, supporting its potential as a lead PTP1B inhibitor. This journal is © The Royal Society of Chemistry, 2026

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Style	Citing Format
MLA	Dastyafteh N, et al.. "Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors." RSC Advances, vol. 16, no. 6, 2026, pp. 5652-5665.
APA	Dastyafteh N, Ghafouri SN, Mollazadeh M, Motamedi Shakib N, Halimi M, Hosseini S, Mojtabavi S, Faramarzi MA, Larijani B, Amanlou M, Mohammadikhanaposhtani M, Mahdavi M (2026). Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors. RSC Advances, 16(6), 5652-5665.
Chicago	Dastyafteh N, Ghafouri SN, Mollazadeh M, Motamedi Shakib N, Halimi M, Hosseini S, Mojtabavi S, et al.. "Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors." RSC Advances 16, no. 6 (2026): 5652-5665.
Harvard	Dastyafteh N et al. (2026) 'Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors', RSC Advances, 16(6), pp. 5652-5665.
Vancouver	Dastyafteh N, Ghafouri SN, Mollazadeh M, Motamedi Shakib N, Halimi M, Hosseini S, et al.. Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors. RSC Advances. 2026;16(6):5652-5665.
BibTex	@article{ author = {Dastyafteh N and Ghafouri SN and Mollazadeh M and Motamedi Shakib N and Halimi M and Hosseini S and Mojtabavi S and Faramarzi MA and Larijani B and Amanlou M and Mohammadikhanaposhtani M and Mahdavi M}, title = {Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors}, journal = {RSC Advances}, volume = {16}, number = {6}, pages = {5652-5665}, year = {2026} }
RIS	TY - JOUR AU - Dastyafteh N AU - Ghafouri SN AU - Mollazadeh M AU - Motamedi Shakib N AU - Halimi M AU - Hosseini S AU - Mojtabavi S AU - Faramarzi MA AU - Larijani B AU - Amanlou M AU - Mohammadikhanaposhtani M AU - Mahdavi M TI - Rational Design and Synthesis of New Acetamide–Indole–Benzo[D]Imidazole–Carboxylic Acid Hybrids As Dual Ptp1b/Α-Glucosidase Inhibitors JO - RSC Advances VL - 16 IS - 6 SP - 5652 EP - 5665 PY - 2026 ER -

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