Evaluation of the interactions of hydrazide derivatives with acetic acid and molecular modeling analysis of N-acetylated hydrazides

Abstract

Acetic acid, as a weak organic acid, has a wide range of food, pharmaceutical, and industrial applications. It is also used as a green solvent, catalyst, and reagent in chemical experiments. Properties such as non-toxicity, safety, availability, and low cost have made it the preferred choice for acetylation processes. In this project, the interactions of a series of alkyl/aryl/heteroaryl hydrazides with acetic acid were investigated under reflux heating. A variety of reactions, including C- and N-acetylation, hydrolysis, and rearrangement, occurred in the presence of acetic acid. Most of the products were recrystallized in good to excellent yields under these conditions without the need for further purification. All synthesized compounds were characterized by NMR (¹H and ¹³C), FT-IR, and CHNS analysis. In addition, a novel method was proposed for the preparation of products 2a and 2i–q. This method has the potential to be extended to similar reagents. To investigate the biological activity and drug-like properties, some in silico methods were employed on the synthesized compounds. Screening using the ChEMBL database revealed that out of 17 synthesized compounds, compounds 2b (ChEMBL93746), 2c (ChEMBL22425), and 2d (ChEMBL441343) exhibited significant activity against targets SIRT1, TPMT, and Tyrosinase, with measured values below 200 μM. Molecular docking demonstrated that compound 2o interacted with all three targets. These findings provide valuable insights into its potential as a promising multi-target drug candidate for future investigations.