Synthesis, Admet Properties, And In Vitro Antimicrobial And Antibiofilm Activity Of 5-Nitro-2-Thiophenecarbaldehyde N-((E)-(5-Nitrothienyl)Methylidene)Hydrazone (Ktu-286) Againststaphylococcus Aureuswith Defined Resistance Mechanisms

The emergence of drug-resistantStaphylococcus aureusis responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance amongS. aureusin the clinical setting. We, therefore, characterized the in silico absorption, distribution, metabolism, elimination, and toxicity (ADMET) and in vitro antimicrobial activity of 5-nitro-2-thiophenecarbaldehyde N-((E)-(5-nitrothienyl)methylidene)hydrazone (KTU-286) against drug-resistantS. aureusstrains with genetically defined resistance mechanisms. The antimicrobial activity of KTU-286 was determined by CLSI recommendations. The ADMET properties were estimated by using in silico modeling. The activity on biofilm integrity was examined by crystal violet assay. KTU-286 demonstrated low estimated toxicity and low skin permeability. The highest antimicrobial activity was observed among pan-susceptible (Pan-S)S. aureus(minimal inhibitory concentration (MIC) 0.5-2.0 mu g/mL, IC50= 0.460 mu g/mL), followed by vancomycin resistantS. aureus(VRSA) (MIC 4.0 mu g/mL, IC50= 1.697 mu g/mL) and methicillin-resistantS. aureus(MRSA) (MIC 1.0-16.0 mu g/mL, IC50= 2.282 mu g/mL). KTU-286 resulted in significant (p< 0.05) loss ofS. aureusbiofilm integrity in vitro. Further studies are needed for a better understanding of safety, synergistic relationship, and therapeutic potency of KTU-286.