Drug screening to identify compounds to act as co-therapies for the treatment of Burkholderia species
Fig 5
Hit expansion around chloroxine.
A B. thailandensis culture was harvested and resuspended to a concentration of 8x108 CFU/mL in M9 media supplemented with 730 μM ceftazidime. This was added to a 96 well plate containing two-fold dilutions of compounds in DMSO from a starting concentration of 1 mM. Plates were incubated for 24 hours at 37°C before addition of the PrestoBlue cell viability reagent and the fluorescence read. Results show three biological replicates with error bars indicating standard deviation. These experiments are equivalent to those in Fig 3 and can be compared to chloroxine in Fig 3. 7-amino-5-chloro-8-quinolinol differs to chloroxine through substitution of an amino group for a chlorine at position 7 (A). This modification causes a significant decrease in this compound’s activity as a co-treatment with ceftazidime, with a pIC50 ≈ 3.4. 5,7-dichloro-2-methyl-8-quinolinol differs from chloroxine by addition of a methyl group in the 2-position (B). This addition abolishes this compound’s activity as a co-treatment with ceftazidime at the concentrations tested. 7-Bromo-8-quinolinol differs from chloroxine by the removal of chlorine at the 5-position, and replacement of chlorine by bromine at the 7-position (C). This compound retains activity as a co-treatment with ceftazidime that is comparable with the parent compound (pIC50 = 5.1, 5.5 for chloroxine).