Design, synthesis, and biological studies of isoniazid-based hydrazone Derivatives: Antibacterial, anticancer, and...

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 K_i constants of 0.020 ± 0.003, 0.019 ± 0.002, and 0.027 ± 0.004 μM respectively. For hCAs acetazoleamide was used as standard inhibitor (having IC₅₀ 0.068 μM and 0.273 μM for hCAI and hCAII) and tacrine was used for AChE with 0.047 μM 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-to-date technique for chemical synthesis and biological evaluation.