TY - JOUR
T1 - 4(1H)-quinolones with liver stage activity against Plasmodium berghei
AU - LaCrue, Alexis N.
AU - Sáenz, Fabián E.
AU - Cross, R. Matthew
AU - Udenze, Kenneth O.
AU - Monastyrskyi, Andrii
AU - Stein, Steven
AU - Mutka, Tina S.
AU - Manetsch, Roman
AU - Kyle, Dennis E.
PY - 2013/1
Y1 - 2013/1
N2 - With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luccon) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.
AB - With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luccon) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.
UR - http://www.scopus.com/inward/record.url?scp=84872007251&partnerID=8YFLogxK
U2 - 10.1128/AAC.00793-12
DO - 10.1128/AAC.00793-12
M3 - Article
C2 - 23129047
AN - SCOPUS:84872007251
SN - 0066-4804
VL - 57
SP - 417
EP - 424
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 1
ER -