Start Date
2018
Description
Bacterial resistance to current antibiotics is a growing problem across the globe. The CDC reported that the estimated minimum illnesses caused by antibiotic resistance in the year 2013 was over 2 million, resulting in about 23,000 deaths in the U.S. 1 In 2014, the Obama administration released an executive order mandating that research be conducted to identify solutions to the bacterial resistance problem, especially in Gram-negative bacteria. One antibiotic series that has shown some promise are the fluoroquinolones. Fluoroquinolones have been on the market for years, with a current reference example being moxifloxacin. Fluoroquinolones (FQs) work by targeting DNA gyrase and topoisomerase IV, which are clinically validated antibacterial targets. Getting antibiotics into Gram-negative bacteria is a multivariate problem. Gram-negative bacteria utilize two membranes, an outer membrane that is hydrophilic, and an inner membrane that is lipophilic. These bacteria also have antibiotic de-activating enzymes and RND efflux pumps that work to remove the antibiotics from the cell. These features make targeting of Gram-negative organisms very difficult. A new drug lead called QPT-1 has been shown to be active against quinolone-resistant bacteria, with low MIC values (MIC90 = 0.5 mg/mL) even against moxifloxacinresistant Staphylococcus aureus. 2 QPT-1 works by interacting with GyrB (in red) instead of GyrA (in blue), moxifloxacin’s target)
Recommended Citation
Burroughs, Luke; Kuperus, Joshua; Medendorp, Evamarie; and Barbachyn, Michael, "Progress Toward the Synthesis of Novel Bacterial Topoisomerase Inhibitors Derived from Fluoroquinolones. N-1 Amine Derivatives" (2018). Summer Research. 11.
https://digitalcommons.calvin.edu/summer_research/2018/Posters/11
Included in
Progress Toward the Synthesis of Novel Bacterial Topoisomerase Inhibitors Derived from Fluoroquinolones. N-1 Amine Derivatives
Bacterial resistance to current antibiotics is a growing problem across the globe. The CDC reported that the estimated minimum illnesses caused by antibiotic resistance in the year 2013 was over 2 million, resulting in about 23,000 deaths in the U.S. 1 In 2014, the Obama administration released an executive order mandating that research be conducted to identify solutions to the bacterial resistance problem, especially in Gram-negative bacteria. One antibiotic series that has shown some promise are the fluoroquinolones. Fluoroquinolones have been on the market for years, with a current reference example being moxifloxacin. Fluoroquinolones (FQs) work by targeting DNA gyrase and topoisomerase IV, which are clinically validated antibacterial targets. Getting antibiotics into Gram-negative bacteria is a multivariate problem. Gram-negative bacteria utilize two membranes, an outer membrane that is hydrophilic, and an inner membrane that is lipophilic. These bacteria also have antibiotic de-activating enzymes and RND efflux pumps that work to remove the antibiotics from the cell. These features make targeting of Gram-negative organisms very difficult. A new drug lead called QPT-1 has been shown to be active against quinolone-resistant bacteria, with low MIC values (MIC90 = 0.5 mg/mL) even against moxifloxacinresistant Staphylococcus aureus. 2 QPT-1 works by interacting with GyrB (in red) instead of GyrA (in blue), moxifloxacin’s target)