Design, Synthesis, and Biological Studies of Isoniazid-Based Hydrazone Derivatives: Antibacterial, Anticancer, and Enzyme Inhibitory Properties

Abstract

Discovery of novel and effective molecules is of vital importance in solving global health problems such as cancer, neurodegenerative diseases and antibiotic resistance. In this study, a series of isoniazid-based hydrazone derivatives were synthesized for the first time via the condensation of isoniazid with structurally diverse aldehydes, including Mannich base, acylated, and sulfonate-containing derivatives. The primary focus was to assess their anticancer properties, antibacterial efficacy, and enzyme inhibition potential, contributing to the development of promising therapeutic agents. In addition, enzyme inhibition mechanisms were predicted by molecular docking methods, structural explanations were made for the biological activities and drug likeness characters of these molecules. The highest inhibitory effects were exhibited by compounds 6a for hCAI, 5b for hCAII, and 6a for AChE with Ki constants of 0.020 f 0.003, 0.019 f 0.002, and 0.027 f 0.004 mu M respectively. For hCAs acetazoleamide was used as standard inhibitor (having IC50 0.068 mu M and 0.273 mu M for hCAI and hCAII) and tacrine was used for AChE with 0.047 mu M IC50. Compound 5b showed the highest binding scores for all enzymes in molecular docking tests having -8.15, -8.56, and -11.09 kcal/mol against CAI, CAII and AChE receptors. For both antibacterial and anticancer research, compound 5b had the most significant outcomes. In particular, mechanistic investigation of antibacterial, anticancer and enzyme inhibition effects will help new treatment options and better understanding of biochemical mechanisms. The study presents a new and up-todate technique for chemical synthesis and biological evaluation.