Identification of small molecule compounds active against Staphylococcus aureus and Proteus mirabilis

Highlights: • Focused library screen identifies bacteriostatics of many pathogens. • Staphylococcus aureus' growth is inhibited at IC₅₀ = 30–150 μM. • Proteus mirabilis is killed by similar compound chemical structures of compounds are different from known antibacterials. Staphylococcus aureus is a human pathogen rapidly becoming a serious health problem due to ease of acquiring antibiotic resistance. To help identify potential new drug candidates effective against the pathogen, a small focused library was screened for inhibition of bacterial growth against several pathogens, including S. aureus. At least one of the compounds, Compound 10, was capable of blocking bacterial growth of S. aureus in a test tube with IC₅₀ = 140 ± 30 μM. Another inhibitor, Compound 7, was bacteriostatic against S. aureus with IC₅₀ ranging from 33 to 150 μM against 3 different strains. However, only Compound 7 was bactericidal against P. mirabilis as examined by electron microscopy. Human cell line toxicity studies suggested that both compounds had small effect on cell growth at 100 μM concentration as examined by MTT assay. Analysis of compounds' structures showed lack of similarity to any known antibiotics and bacteriostatics, potentially offering the inhibitors as an alternative to existing solutions in controlling bacterial infections for selected pathogens.