Design and synthesis of vanillin-mediated hydrazine derivatives as multi-bioactive drug development

To synthesize and characterize vanillin-mediated hydrazine derivatives (1a-j) and evaluate their in vitro antibacterial, antioxidant, and cytotoxic activities. This study is further supported by molecular docking, MD simulation, and DFT calculation studies.

A series of one-pot multi-component Mannich-base vanillin-mediated hydrazine derivatives (1a-j) were synthesized and characterized by NMR, FTIR, and MS. The resulting compounds were subjected to in vitro studies, and the active compounds were further subjected to molecular docking using AutoDock Vina 1.1.2 and Discovery Studio. Molecular dynamics simulations via Desmond were performed to assess the docked complex stability, whereas DFT calculations were done using Gaussian 9.0.

Compound 1j exhibited the highest activity against ESBLKP and ESBLEC compared to standard antibiotics in antibacterial activity, whereas 1c, 1d, and 1f demonstrated higher antioxidant activity relative to the standard. Highly active compounds 1j and 1f were further investigated for computational studies. Docking studies indicated favorable binding sites stabilized through hydrogen bonds and hydrophobic or halogen interactions at crucial residues.

In this study, compounds 1d, 1f, and 1j exhibited significant antimicrobial and antioxidant activities. These findings highlight the necessity for structural optimization to enhance their efficacy and specificity, and recommend further mechanistic studies.