In Silico Docking and Spectroscopic Evaluation of a Thiocarbohydrazone Derivative: Structural Elucidation and Enzyme Inhibitory Mechanisms.

Objectives

Thiocarbohydrazones represent an important class of Schiff base derivatives with versatile chemical and biological properties.

Methods

Herein, we present a combined in silico spectroscopic and molecular docking investigation of N'-benzylidenehydrazinecarbothiohydrazide (1).

Results

Conformational docking studies were conducted against cathepsin B, acetylcholinesterase, HER2, protein kinase C, and protein kinase A. The compound displayed favorable binding affinities and key interactions within the catalytic sites of all targets, with the strongest predicted binding observed for acetylcholinesterase. Notably, all conformers exhibited higher affinity for protein kinase C than the reference inhibitor balanol, and hydroxylation led to an approximately 10% enhancement in docking performance. Density functional theory (DFT) calculations were employed to analyze vibrational properties, and IR and Raman spectra were computed to elucidate structural features and conformational behavior.

Conclusions

The integrated spectroscopic and docking analyses provide mechanistic insights into ligand-target interactions and support rational drug design. These findings identify thiocarbohydrazone derivatives as promising multi-target candidates for the development of enzyme inhibitors relevant to neurodegenerative, oncological, and inflammatory diseases.