RRC ID 57059
Author Kwofie KD, Sato K, Sanjoba C, Hino A, Shimogawara R, Amoa-Bosompem M, Ayi I, Boakye DA, Anang AK, Chang KS, Ohashi M, Kim HS, Ohta N, Matsumoto Y, Iwanaga S.
Title Oral activity of the antimalarial endoperoxide 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Leishmania donovani complex.
Journal PLoS Negl Trop Dis
Abstract Visceral leishmaniasis (VL) is a major problem worldwide and causes significant morbidity and mortality. Existing drugs against VL have limitations, including their invasive means of administration long duration of treatment regimens. There are also concerns regarding increasing treatment relapses as well as the identification of resistant clinical strains with the use of miltefosine, the sole oral drug for VL. There is, therefore, an urgent need for new alternative oral drugs for VL. In the present study, we show the leishmanicidal effect of a novel, oral antimalarial endoperoxide N-251. In our In vitro studies, N-251 selectively and specifically killed Leishmania donovani D10 amastigotes with no accompanying toxicity toward the host cells. In addition, N-251 exhibited comparable activities against promastigotes of L. donovani D10, as well as other L. donovani complex parasites, suggesting a wide spectrum of activity. Furthermore, even after a progressive infection was established in mice, N-251 significantly eliminated amastigotes when administered orally. Finally, N-251 suppressed granuloma formation in mice liver through parasite death. These findings indicate the therapeutic effect of N-251 as an oral drug, hence suggest N-251 to be a promising lead compound for the development of a new oral chemotherapy against VL.
Volume 13(3)
Pages e0007235
Published 2019-3
DOI 10.1371/journal.pntd.0007235
PII PNTD-D-18-01712
PMID 30908481
PMC PMC6433226
MeSH Animals Antimalarials / administration & dosage* Antimalarials / pharmacology Antiprotozoal Agents / administration & dosage* Antiprotozoal Agents / pharmacology Cell Survival / drug effects Disease Models, Animal Leishmania donovani / drug effects* Leishmania donovani / physiology Leishmaniasis, Visceral / drug therapy* Leishmaniasis, Visceral / pathology Liver / pathology Mice, Inbred BALB C Spiro Compounds / administration & dosage* Spiro Compounds / pharmacology Tetraoxanes / administration & dosage* Tetraoxanes / pharmacology Treatment Outcome
IF 4.367
Resource
Pathogenic eukaryotic microorganisms 病原原虫:Ld003