Evaluation in vitro and in silico of LIG08, a benzoxathiolone-thiazolidinone derivative, as a potential drug against Klebsiella pneumoniae

Abstract Infectious diseases represent one of the most critical and urgent global health challenges. However, the misuse of antibiotics has enhanced this issue, raising concerns about treatment effectiveness, particularly in the face of the emergence of antibiotic-resistant bacterial strains. In this context, the research for new antimicrobial compounds becomes imperative. Here, synthetic benzoxathiolone-thiazolidinone hybrids emerged as promising molecules that combat infections caused by the resistant bacteria Klebsiella pneumonia . The results demonstrated a promising antibacterial effect of LIG08 (MIC 50 44.87 µM), which caused damage to the cell membrane and overproduction of reactive oxygen species (ROS) (MIC 50 /2, MIC 50 , and 2xMIC 50 ), and damage to cell morphology at MIC 50 . In silico analysis predicted low toxicity for LIG08 and desirable pharmacokinetic parameters. Target fishing analysis predicted that LIG08 strongly interacts with Mannose-6-phosphate isomerase (M6PI), a central enzyme for the bacterial energetic and cell wall structural metabolism. Altogether, these results suggested that LIG08 is a potential antibacterial molecule that can be further investigated as an alternative molecule to fight back against bacterial infections.