Synthesis and Evaluation of Troponoids as a New Class of Antibiotics

Feng Cao; Cari Orth; Maureen J. Donlin; Patrick Adegboyega; Marvin J. Meyers; Ryan P. Murelli; Mohamed Elagawany; Bahaa Elgendy; John E. Tavis

doi:10.1021/acsomega.8b01754

Synthesis and Evaluation of Troponoids as a New Class of Antibiotics

Feng Cao
, Cari Orth
, Maureen J. Donlin
, Patrick Adegboyega
, Marvin J. Meyers
, Ryan P. Murelli
, Mohamed Elagawany
, Bahaa Elgendy
, John E. Tavis

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	15125-15133
Number of pages	9
Journal	ACS Omega
Volume	3
Issue number	11
DOIs	https://doi.org/10.1021/acsomega.8b01754
State	Published - Nov 8 2018

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title = "Synthesis and Evaluation of Troponoids as a New Class of Antibiotics",

abstract = "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.",

author = "Feng Cao and Cari Orth and Donlin, \{Maureen J.\} and Patrick Adegboyega and Meyers, \{Marvin J.\} and Murelli, \{Ryan P.\} and Mohamed Elagawany and Bahaa Elgendy and Tavis, \{John E.\}",

note = "Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

year = "2018",

month = nov,

day = "8",

doi = "10.1021/acsomega.8b01754",

language = "English",

volume = "3",

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T1 - Synthesis and Evaluation of Troponoids as a New Class of Antibiotics

AU - Cao, Feng

AU - Orth, Cari

AU - Donlin, Maureen J.

AU - Adegboyega, Patrick

AU - Meyers, Marvin J.

AU - Murelli, Ryan P.

AU - Elagawany, Mohamed

AU - Elgendy, Bahaa

AU - Tavis, John E.

PY - 2018/11/8

Y1 - 2018/11/8

N2 - 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.

AB - 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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DO - 10.1021/acsomega.8b01754

M3 - Article

AN - SCOPUS:85056296402

SN - 2470-1343

VL - 3

SP - 15125

EP - 15133

JO - ACS Omega

JF - ACS Omega

IS - 11

ER -

Synthesis and Evaluation of Troponoids as a New Class of Antibiotics

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