Synthesis of modified Schiff base appended 1,2,4-triazole hybrids scaffolds: elucidating the in vitro and in silico α-amylase and α-glucosidase inhibitors potential

Shahzad Ahmad Abbasi; Fazal Rahim; Rafaqat Hussain; Wajid Rehman; Shoaib Khan; Muhammad Taha; Tayyiaba Iqbal; Yousaf Khan; Syed Adnan Ali Shah

doi:10.1515/znc-2024-0073

Artikel

Synthesis of modified Schiff base appended 1,2,4-triazole hybrids scaffolds: elucidating the in vitro and in silico α-amylase and α-glucosidase inhibitors potential

Shahzad Ahmad Abbasi , Fazal Rahim , Rafaqat Hussain , Wajid Rehman , Shoaib Khan , Muhammad Taha , Tayyiaba Iqbal , Yousaf Khan und Syed Adnan Ali Shah

Veröffentlicht/Copyright: 12. Juli 2024

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Abstract

The current study involves the synthesis of Schiff bases based on 1,2,4-triazoles skeleton and assessing their α-amylase and α-glucosidase profile. Furthermore, the precise structures of the synthesized derivatives were elucidated using various spectroscopic methods such as ¹H-NMR, ¹³C-NMR and HREI-MS. Using glimepiride as the reference standard, the in vitro α-glucosidase and α-amylase inhibitory activities of the synthesized compounds were evaluated in order to determine their potential anti-diabetic properties. All analogues showed varied range of inhibitory activity having IC₅₀ values ranging from 17.09 ± 0.72 to 45.34 ± 0.03 μM (α-amylase) and 16.35 ± 0.42 to 42.31 ± 0.09 μM (α-glucosidase), respectively. Specifically, the compounds 1, 7 and 8 were found to be significantly active with IC₅₀ values of 17.09 ± 0.72, 19.73 ± 0.42, and 23.01 ± 0.04 μM (against α-amylase) and 16.35 ± 0.42, 18.55 ± 0.26, and 20.07 ± 0.02 μM (against α-glucosidase) respectively. The obtained results were compared with the Glimepiride reference drug having IC₅₀ values of 13.02 ± 0.11 μM (for α-glucosidase) and 15.04 ± 0.02 μM (for α-amylase), respectively. The structure–activity relationship (SAR) studies were conducted based on differences in substituent patterns at varying position of aryl rings A and B may cause to alter the inhibitory activities of both α-amylase and α-glucosidase enzymes. Additionally, the molecular docking study was carried out to explore the binding interactions possessed by most active analogues with the active sites of targeted α-amylase and α-glucosidase enzymes.

Keywords: synthesis; α-amylase; α-glucosidase; triazole; SAR and molecular docking

Corresponding authors: Fazal Rahim and Rafaqat Hussain, Department of Chemistry, Hazara University, Mansehra, 21120, Pakistan, E-mail: fazalstar@gmail.com (F. Rahim), rafaqathussain0347@gmail.com (R. Hussain)

Research ethics: The conducted research is not related to either human or animal use.
Author contributions: Shahzad Ahmad Abbasi: writing – original draft. Fazal Rahim & Wajid Rehman: supervision. Rafaqat Hussain & Shoaib Khan: writing – review and editing. Yousaf Khan: methodology and investigation. Tayyiaba Iqbal: visualization and software. Muhammad Taha & Syed Adnan Ali Shah: characterization.
Competing interests: The authors declare no conflict of interest.
Research funding: None declared.
Data availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2024-04-04

Accepted: 2024-06-20

Published Online: 2024-07-12

Published in Print: 2025-03-26

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https://doi.org/10.1515/znc-2024-0073

Schlagwörter für diesen Artikel

synthesis; α-amylase; α-glucosidase; triazole; SAR and molecular docking