Inhibitory effect ofN-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide onHaemophilusspp. planktonic or biofilm-forming cells.
During this study, we have investigated in vitro activity ofN-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives withN-ethyl,N-(4-metoxyphenyl) andN-cyclohexyl substituents against Gram-negativeHaemophilus influenzaeandH.parainfluenzaebacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the testedN-substituted pyrazole derivatives, onlyN-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells ofH.parainfluenzae(MIC = 0.49-31.25 μg ml-1) andH.influenzae(MIC = 0.24-31.25 μg ml-1) as well as biofilm-forming cells ofH.parainfluenzae(MBIC = 0.24-31.25 μg ml-1) andH. influenzae(MBIC = 0.49 to ≥31.25 μg ml-1). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates ofH. parainfluenzaethan the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazoleN-ethyl derivative could be considered as a compound for the design of agents active against both pathogenicH. influenzaeand opportunisticH. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy.
Department of Pharmaceutical Microbiology, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland.
Urszula
U
Kosikowska
Department of Pharmaceutical Microbiology, Medical University of Lublin, Chodzki Str. 1, 20-093 Lublin, Poland.
Anna
A
Malm
Department of Organic Chemistry, Medical University, Chodzki Str. 4a, 20-093 Lublin, Poland.
Monika
M
Pitucha
Department of Virology, Medical University, Chodzki Str. 1, 20-093 Lublin, Poland.
Barbara
B
Rajtar
Department of Virology, Medical University, Chodzki Str. 1, 20-093 Lublin, Poland.
Malgorzata
M
Polz-Dacewicz
Anti-biofilm activity; Antibacterial activity; Cytotoxicity; Haemophilus spp.; Pyrazole derivatives