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

There is an increasing prevalence of diabetes mellitusthroughoutthe world, and new compounds are necessary to combat this. The currentlyavailable antidiabetic therapies are long-term complicated and sideeffect-prone, and this has led to a demand for more affordable andmore effective methods of tackling diabetes. Research is focused onfinding alternative medicinal remedies with significant antidiabeticefficacy as well as low adverse effects. In this research work, wehave focused our efforts to synthesize a series of 1,2,4-triazole-basedbis-hydrazones and evaluated their antidiabetic properties. In addition,the precise structures of the synthesized derivatives were confirmedwith the help of various spectroscopic techniques including H-1-NMR, C-13-NMR, and HREI-MS. To find the antidiabeticpotentials of the synthesized compounds, in vitro alpha-glucosidaseand alpha-amylase inhibitory activities were characterized usingacarbose as the reference standard. From structure-activity(SAR) analysis, it was confirmed that any variation found in inhibitoryactivities of both alpha-amylase and alpha-glucosidase enzymeswas due to the different substitution patterns of the substituent(s)at variable positions of both aryl rings A and B. The results of theantidiabetic assay were very encouraging and showed moderate to goodinhibitory potentials with IC50 values ranging from 0.70 +/- 0.05 to 35.70 +/- 0.80 mu M (alpha-amylase) and 1.10 +/- 0.05 to 30.40 +/- 0.70 mu M (alpha-glucosidase). Theobtained results were compared to those of the standard acarbose drug(IC50 = 10.30 +/- 0.20 mu M for alpha-amylaseand IC50 = 9.80 +/- 0.20 mu M for alpha-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 mu M against alpha-amylase and 1.10 +/- 0.05, 1.50 +/- 0.05, and 1.70 +/- 0.10 mu M against alpha-glucosidase, respectively.These findings reveal that triazole-containing bis-hydrazones actas alpha-amylase and alpha-glucosidase inhibitors, which helpdevelop novel therapeutics for treating type-II diabetes mellitusand can act as lead molecules in drug discovery as potential antidiabeticagents.