4(1H)-Quinolones with Liver Stage Activity against Plasmodium berghei

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Published inAntimicrobial Agents and Chemotherapy Vol. 57; no. 1; pp. 417 - 424
Main Authors LACRUE, Alexis N, SAENZ, Fabián E, CROSS, R. Matthew, UDENZE, Kenneth O, MONASTYRSKYI, Andrii, STEIN, Steven, MUTKA, Tina S, MANETSCH, Roman, KYLE, Dennis E
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.01.2013
Subjects
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials
Antimalarials - chemical synthesis
Antimalarials - pharmacology
Biological and medical sciences
Female
Genes, Reporter
Hep G2 Cells
Hepatocytes - drug effects
Hepatocytes - parasitology
Humans
Inhibitory Concentration 50
Kinetics
Liver - drug effects
Liver - parasitology
Luciferases
Malaria
Malaria - drug therapy
Malaria - parasitology
Medical sciences
Mice
Mice, Inbred BALB C
Organisms, Genetically Modified
Pharmacology. Drug treatments
Plasmodium berghei
Plasmodium berghei - drug effects
Plasmodium berghei - genetics
Plasmodium berghei - growth & development
Quinolones
Quinolones - chemical synthesis
Quinolones - pharmacology
Sporozoites
Sporozoites - drug effects
Sporozoites - growth & development
Susceptibility
Protozoa
Apicomplexa
Plasmodium berghei
Clinical stage
Liver
Antibacterial agent
Biological activity
Quinolone derivatives
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Abstract Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to AAC .asm.org, visit: AAC       
AbstractList 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-Luc(con)) 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.
Classifications Services AAC Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to AAC .asm.org, visit: AAC       
ABSTRACT 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; Pb GFP-Luc con ) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1 H )-quinolone (PEQ), as well as two 3-phenyl-4(1 H )-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.
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.
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; Pb GFP-Luc con ) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1 H )-quinolone (PEQ), as well as two 3-phenyl-4(1 H )-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.
Author Steven Stein
Roman Manetsch
Fabián E. Sáenz
Andrii Monastyrskyi
Dennis E. Kyle
Tina S. Mutka
Alexis N. LaCrue
Kenneth O. Udenze
R. Matthew Cross
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  surname: KYLE
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  organization: Department of Global Health, University of South Florida, Tampa, Florida, United States
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Copyright © 2013, American Society for Microbiology. All Rights Reserved.
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Issue 1
Keywords Protozoa
Apicomplexa
Plasmodium berghei
Clinical stage
Liver
Antibacterial agent
Biological activity
Quinolone derivatives
Language English
License CC BY 4.0
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Notes A.N.L. and F.S. contributed equally to this article.
Present address: Fabián Sáenz, Centro de Investigación en Enfermedades Infecciosas, Escuela de Ciencias Biológicas, Pontificia Universidad Católica del Ecuador, Quito, Ecuador.
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PublicationTitle Antimicrobial Agents and Chemotherapy
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With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic...
ABSTRACT With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a...
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SourceType Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage 417
SubjectTerms Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials
Antimalarials - chemical synthesis
Antimalarials - pharmacology
Biological and medical sciences
Female
Genes, Reporter
Hep G2 Cells
Hepatocytes - drug effects
Hepatocytes - parasitology
Humans
Inhibitory Concentration 50
Kinetics
Liver - drug effects
Liver - parasitology
Luciferases
Malaria
Malaria - drug therapy
Malaria - parasitology
Medical sciences
Mice
Mice, Inbred BALB C
Organisms, Genetically Modified
Pharmacology. Drug treatments
Plasmodium berghei
Plasmodium berghei - drug effects
Plasmodium berghei - genetics
Plasmodium berghei - growth & development
Quinolones
Quinolones - chemical synthesis
Quinolones - pharmacology
Sporozoites
Sporozoites - drug effects
Sporozoites - growth & development
Susceptibility
Title 4(1H)-Quinolones with Liver Stage Activity against Plasmodium berghei
URI http://aac.asm.org/content/57/1/417.abstract
https://www.ncbi.nlm.nih.gov/pubmed/23129047
https://journals.asm.org/doi/10.1128/AAC.00793-12
https://pubmed.ncbi.nlm.nih.gov/PMC3535941
Volume 57
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