Synthesis and In Vitro α-Amylase and α-Glucosidase Dual Inhibitory Activities of 1,2,4-Triazole-Bearing bis-Hydrazone Derivatives and Their Molecular Docking Study

Imran Khan; Wajid Rehman; Fazal Rahim; Rafaqat Hussain; Shoaib Khan; Liaqat Rasheed; Mohammed M Alanazi; Ashwag S Alanazi; Magda H Abdellattif

doi:10.1021/acsomega.3c00702

Synthesis and In Vitro α-Amylase and α-Glucosidase Dual Inhibitory Activities of 1,2,4-Triazole-Bearing bis-Hydrazone Derivatives and Their Molecular Docking Study

ACS Omega. 2023 Jun 5;8(25):22508-22522. doi: 10.1021/acsomega.3c00702. eCollection 2023 Jun 27.

Authors

Imran Khan¹, Wajid Rehman¹, Fazal Rahim¹, Rafaqat Hussain¹, Shoaib Khan¹, Liaqat Rasheed¹, Mohammed M Alanazi², Ashwag S Alanazi³, Magda H Abdellattif⁴

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
³ Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P. O. Box 84428, Riyadh 11671, Saudi Arabia.
⁴ Department of Chemistry, College of Sciences, Taif University, P. O. Box 11099, Taif 21944, Saudi Arabia.

Abstract

There is an increasing prevalence of diabetes mellitus throughout the world, and new compounds are necessary to combat this. The currently available antidiabetic therapies are long-term complicated and side effect-prone, and this has led to a demand for more affordable and more effective methods of tackling diabetes. Research is focused on finding alternative medicinal remedies with significant antidiabetic efficacy as well as low adverse effects. In this research work, we have focused our efforts to synthesize a series of 1,2,4-triazole-based bis-hydrazones and evaluated their antidiabetic properties. In addition, the precise structures of the synthesized derivatives were confirmed with the help of various spectroscopic techniques including ¹H-NMR, ¹³C-NMR, and HREI-MS. To find the antidiabetic potentials of the synthesized compounds, in vitro α-glucosidase and α-amylase inhibitory activities were characterized using acarbose as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both α-amylase and α-glucosidase enzymes was due to the different substitution patterns of the substituent(s) at variable positions of both aryl rings A and B. The results of the antidiabetic assay were very encouraging and showed moderate to good inhibitory potentials with IC₅₀ values ranging from 0.70 ± 0.05 to 35.70 ± 0.80 μM (α-amylase) and 1.10 ± 0.05 to 30.40 ± 0.70 μM (α-glucosidase). The obtained results were compared to those of the standard acarbose drug (IC₅₀ = 10.30 ± 0.20 μM for α-amylase and IC₅₀ = 9.80 ± 0.20 μM for α-glucosidase). Specifically, compounds 17, 15, and 16 were found to be significantly active with IC₅₀ values of 0.70 ± 0.05, 1.80 ± 0.10, and 2.10 ± 0.10 μM against α-amylase and 1.10 ± 0.05, 1.50 ± 0.05, and 1.70 ± 0.10 μM against α-glucosidase, respectively. These findings reveal that triazole-containing bis-hydrazones act as α-amylase and α-glucosidase inhibitors, which help develop novel therapeutics for treating type-II diabetes mellitus and can act as lead molecules in drug discovery as potential antidiabetic agents.