Benzylidenehydrazine Derivatives: Synthesis, Antidiabetic Evaluation, Antioxidation, Mode of Inhibition, DFT and Molecular Docking Studies

Nov 12, 2024Chemistry & biodiversity

Creation and Testing of Benzylidenehydrazine Compounds for Diabetes Control, Antioxidant Effects, and How They Work Using Computer Models

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Abstract

The compound 9 demonstrated an IC value of 116.19 μM as the strongest inhibitor of α-amylase.

Benzylidenehydrazine derivatives were synthesized and evaluated for their ability to inhibit α-glucosidase and α-amylase.
All synthesized derivatives exhibited greater inhibitory potency against α-amylase compared to α-glucosidase.
Compound 9 showed approximately 5-fold superior activity against α-amylase compared to the standard drug, acarbose.
Compounds 18 and 19 exhibited strong nitric oxide scavenging activity, outperforming Trolox.
Kinetic studies revealed that compound 9 functions as a non-competitive inhibitor of α-amylase.
Molecular docking and density functional theory studies were performed for compound 9 to analyze its structural properties and interactions.

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Diabetes mellitus (DM) is a metabolic condition that is a profound health concern across the globe due to its contribution to the increased mortality rate. It affects millions of people around the world and is associated with severe complications among people diagnosed with it. Among the array of approaches used for the management of DM, inhibition of enzymes viz. α-amylase and α-glucosidase which are responsible for sugars hydrolysis is regarded as a feasible therapeutic protocol for the management of DM. Herein, we report the synthesis of benzylidenehydrazine derivatives as well as their evaluation as α-glucosidase and α-amylase inhibitors including their antioxidant testing. Generally, all the synthesized derivatives were more potent inhibitors of α-amylase than of α-glucosidase. Specifically, 2,4 fluoro substituted analogue 9 (IC=116.19 μM) emerged as the strongest α-amylase inhibitor with ~5-fold superior activity in comparison to the standard drug, acarbose (IC=600 μM). Compounds 18 (IC=240.59) and 19 (IC=198.32 μM) displayed the strongest NO scavenging activity compared to Trolox (IC=272.36 μM). In addition, the enzyme kinetic studies indicated that compound 9 acts as a non-competitive inhibitor of α-amylase. Finally, density functional theory and molecular docking studies for compound 9 were conducted to explore its structural and electronic properties as well as to determine protein-ligand interactions, respectively to decipher its observed activity. The obtained findings present promising possibilities for developing new drug candidates to control postprandial glucose levels in persons with diabetes. 50 50 50 50 50

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5×

Increase in α-amylase inhibition

Comparison of compound 9's IC value to acarbose

240.59 μM

Strong nitric oxide scavenging activity

IC value of compound 18 in nitric oxide assay

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Benzylidenehydrazine Derivatives: Synthesis, Antidiabetic Evaluation, Antioxidation, Mode of Inhibition, DFT and Molecular Docking Studies

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