ao8b01754_si_001.pdf (1.13 MB)
Synthesis and Evaluation of Troponoids as a New Class of Antibiotics
journal contribution
posted on 2018-11-08, 18:37 authored by Feng Cao, Cari Orth, Maureen J. Donlin, Patrick Adegboyega, Marvin J. Meyers, Ryan P. Murelli, Mohamed Elagawany, Bahaa Elgendy, John E. TavisNovel 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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CC 5018 methicillin-resistant SAntibiotics Novel antibioticsMDR-AAcinetobacter baumanniianti-bacterial activityMIC 80New ClassMIC 80 valuesα- HT92 troponoidsPreliminary hitsEscherichia colireference straintropolonenovel troponoid antibioticsStaphylococcus aureushepatoma cellsMRSAPseudomonas aeruginosacombat MDR
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