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Synthesis and Evaluation of Troponoids as a New Class of Antibiotics.
ACS Omega 2018 November 31
Novel antibiotics are urgently needed. The troponoids [tropones, tropolones, and α-hydroxytropolones (α-HT)] can have anti-bacterial activity. We synthesized or purchased 92 troponoids and evaluated their antibacterial activities against Staphylococcus aureus , Escherichia coli , Acinetobacter baumannii, and Pseudomonas aeruginosa . Preliminary hits were assessed for minimum inhibitory concentrations (MIC80 ) and cytotoxicity (CC50 ) against human hepatoma cells. Sixteen troponoids inhibited S. aureus / E. coli / A. baumannii growth by ≥80% growth at <30 μM with CC50 values >50 μM. Two selected tropolones ( 63 and 285 ) inhibited 18 methicillin-resistant S. aureus (MRSA) strains with similar MIC80 values as against a reference strain. Two selected thiotropolones ( 284 and 363 ) inhibited multidrug-resistant (MDR) E. coli with MIC80 ≤30 μM. One α-HT ( 261 ) inhibited MDR- A. baumannii with MIC80 ≤30 μM. This study opens new avenues for development of novel troponoid antibiotics to address the critical need to combat MDR bacterial infections.
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