Green Synthesis, Spectral Characterization, In Silico and In Vitro Antimicrobial Investigations, and ADMET Profiling of Functionalized Hydrazone Derivatives

In an effort to develop new antimicrobials, we report a green and rapid synthetic procedure that leads to the formation of functionalized hydrazone derivatives through a one-pot reaction of various aromatic and heteroaromatic aldehydes with phenylhydrazine. The identification of the produced product structures was achieved through spectroscopic data. The preliminary biological assessment of antimicrobial activity indicated that analogs 3c and 3l exhibit higher activity than the commercial antibiotic streptomycin against S. aureus and P. aeruginosa test organisms, respectively. In in silico molecular docking studies, analog 3l exhibits higher docking scores of –8.3 and –6.9 kcal/mol against P. aeruginosa and S. aureus, respectively, than streptomycin (a reference compound) and other synthesized analogs. The predictive absorption–distribution–metabolism–excretion–toxicity (ADMET) profiles of the most active analogs confirm their remarkable drug-likeness and good pharmacokinetic properties.