Synthesis, biological evaluation, and molecular docking of benzhydrazide derivatives

Abstract

In the pursuit of discovering and developing compounds with antioxidant and other biological activities, we designed, synthesized, and evaluated 10 hydrazide-hydrazone derivatives of 4-hydroxybenzohydrazide (ohbh1-10) as potential antioxidants. The compounds were synthesized using a Milestone FlexiWave microwave reactor, which significantly reduced reaction times and improved product yields. The radical-scavenging activities of the synthesized derivatives were assessed through DPPH and ABTS assays, revealing moderate antioxidant activity compared to the standard antioxidant, Trolox. To explore their potential biological applications, molecular docking simulations were performed to evaluate the binding affinities of the hydrazide- hydrazones within the active sites of monoamine oxidase B (MAO-B) and acetylcholinesterase (AChE). The in silico studies indicated that ohbh10 could act as a dual inhibitor of MAO-B and AChE. Additionally, ADME predictions for ohbh10 demonstrated favorable pharmacokinetic properties, including good blood-brain barrier (BBB) permeability and gastrointestinal absorption. Future work will focus on introducing additional hydroxyl groups into the molecular framework to enhance radical-scavenging properties. Furthermore, the molecular docking results will be validated through in vitro experiments to confirm the dual inhibitory potential of ohbh10 against MAO-B and AChE.