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ACS Omega. 2018 Nov 30;3(11):15125-15133. doi: 10.1021/acsomega.8b01754. Epub 2018 Nov 8.

Synthesis and Evaluation of Troponoids as a New Class of Antibiotics.

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John Cochran Division, Department of Veterans Affairs Medical Center, 915 North Grand Blvd., St. Louis, Missouri 63106, United States.
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, United States.
Department of Chemistry, Saint Louis University, St. Louis, Missouri 63104, United States.
Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York 11210, United States.
PhD Program in Chemistry, The Graduate Center of The City University of New York, New York 10016, United States.
Center for Clinical Pharmacology, Washington University School of Medicine and St. Louis College of Pharmacy, St. Louis, Missouri 63110, United States.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Damanhour University, Damanhour 31111, Egypt.
Chemistry Department, Faculty of Science, Benha University, Benha 13518, Egypt.
Department of Molecular Microbiology and Immunology, The Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, Missouri 63104, United States.


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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