In vitro activity of wALADin benzimidazoles against different life cycle stages of Plasmodium parasites

wALADin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μM, respectively). O...

Full description

Saved in:
Bibliographic Details
Published inAntimicrobial agents and chemotherapy Vol. 59; no. 1; pp. 654 - 658
Main Authors Lentz, Christian S, Sattler, Julia M, Fendler, Martina, Gottwalt, Simon, Halls, Victoria S, Strassel, Silke, Arriens, Sandra, Hannam, Jeffrey S, Specht, Sabine, Famulok, Michael, Mueller, Ann-Kristin, Hoerauf, Achim, Pfarr, Kenneth M
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.01.2015
Subjects
Antimalarials
Antimalarials - pharmacology
Benzimidazoles
Benzimidazoles - chemistry
Benzimidazoles - pharmacology
Experimental Therapeutics
Humans
Inhibitory Concentration 50
Nematoda
Plasmodium berghei
Plasmodium berghei - drug effects
Plasmodium falciparum
Plasmodium falciparum - drug effects
Plasmodium falciparum - physiology
Porphobilinogen Synthase
Porphobilinogen Synthase - antagonists & inhibitors
Thiophenes - chemistry
Thiophenes - pharmacology
Toxoplasma - drug effects
Wolbachia
Online AccessGet full text

Cover

More Information
Summary:wALADin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μM, respectively). One of these derivatives inhibited gliding motility of Plasmodium berghei ANKA infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic replication. Hence, wALADin1 benzimidazoles are tools to study gliding motility and potential antiplasmodial drug candidates.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Citation Lentz CS, Sattler JM, Fendler M, Gottwalt S, Halls VS, Strassel S, Arriens S, Hannam JS, Specht S, Famulok M, Mueller A-K, Hoerauf A, Pfarr KM. 2015. In vitro activity of wALADin benzimidazoles against different life cycle stages of Plasmodium parasites. Antimicrob Agents Chemother 59:654–658. doi:10.1128/AAC.02383-14.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.02383-14