Design, synthesis, and biological evaluation of novel vanillin-derived hydrazone compounds with antimicrobial, anticancer, and enzyme inhibition activities, along with molecular structure and drug-likeness assessment

Abstract

Vanillin-based compounds have recently gained attention in pharmaceutical chemistry as a novel class of organic molecules, demonstrating significant potential as drug candidates for various therapeutic applications. In this study, five novel bioactive Vanillin hydrazones (Van₁ to Van₅) were synthesized and characterized. The synthesized compounds were evaluated for their anticancer activity against MDA-MB-231 breast cancer cells, acetylcholinesterase (AChE) inhibitory effects, antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli, as well as their biofilm inhibition against Pseudomonas aeruginosa. Furthermore, in silico studies were performed to elucidate their molecular interactions. Among the compounds, Van₂ exhibited remarkable anticancer properties, reducing cell viability to below 40 % at a concentration of 50 μg/mL. In terms of AChE inhibition, Van₁ demonstrated significant activity, achieving 50 % inhibition at a concentration of 10 mg/mL. Regarding antibacterial activity, Van₃ was the most effective compound against S. aureus, with a minimum inhibitory concentration (MIC) of 31.25 mg/mL. Van₃ and Van₅ displayed the highest activity against E. faecalis, both with an MIC value of 31.25 mg/mL. Similarly, Van₃ exhibited the strongest antibacterial activity against E. coli, with an MIC value of 31.25 mg/mL. Molecular docking studies revealed significant binding affinities of Van₃ with target proteins 1EVE, 4EY7, 1JIJ, 6QXS, 3NU7, and 6KZV, achieving docking scores of -9.215, -9.399, -6.618, -6.713, -6.682, and -6.048 kcal/mol, respectively.

Keywords: AChE; Antibacterial; Biofilm; Breast cancer; Molecular docking; Vanillin hydrazones.