In Vitro and In Silico Characterization of Novel Fluorobenzhydrazide Deriva-tives With Antibacterial Potential

The search for new compounds with antibacterial activity is of critical importance in modern medicine. The rise of antibiotic-resistant bacteria poses a serious global health threat, making it increasingly difficult to treat common infections. Discovering novel antibacterial agents can help combat these resistant strains and ensure effective treatment options remain available. In this study, eighteen novel fluorobenzhydrazide derivatives, including linear thiosemicarbazides and cyclic 1,2,4-triazoles, were synthesized and evaluated for their in vitro antibacterial activity against various bacterial strains. Among the synthesized compounds, thiosemicarbazide 6, which contains a diethylaminophenyl substituent, exhibited moderate antibacterial activity, particularly against Gram-positive bacteria. This thiosemicarbazide successfully inhibited the growth of all Staphyloccocus aureus strains with an MIC of 64 µg/mL. To explore the potential antibacterial mechanism, molecular docking and molecular dynamics simulations were performed to assess the interaction of these compounds with Ddl ligase and DNA gyrase. Notably, 4-(4-N,N-diethylaminophenyl)-1-(3-fluorobenzoyl)thiosemicarbazide demonstrated a binding mode comparable to that of a known inhibitor, highlighting its potential as a lead compound and suggesting possible directions for further structural modifications.