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.

Autor: Kwofie KD; Section of Environmental Parasitology, Graduate School of Medical Dental Sciences, Tokyo Medical Dental University, Bunkyo-ku, Tokyo, Japan.; Laboratory of Molecular Immunology, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Sato K; Laboratory of Molecular Immunology, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Sanjoba C; Laboratory of Molecular Immunology, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Hino A; Section of Environmental Parasitology, Graduate School of Medical Dental Sciences, Tokyo Medical Dental University, Bunkyo-ku, Tokyo, Japan., Shimogawara R; Section of Environmental Parasitology, Graduate School of Medical Dental Sciences, Tokyo Medical Dental University, Bunkyo-ku, Tokyo, Japan., Amoa-Bosompem M; Section of Environmental Parasitology, Graduate School of Medical Dental Sciences, Tokyo Medical Dental University, Bunkyo-ku, Tokyo, Japan., Ayi I; Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana., Boakye DA; Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana., Anang AK; Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana., Chang KS; Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, Republic of Korea., Ohashi M; Section of Environmental Parasitology, Graduate School of Medical Dental Sciences, Tokyo Medical Dental University, Bunkyo-ku, Tokyo, Japan., Kim HS; Division of International Infectious Disease Control, Faculty of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry Pharmaceutical Sciences, Okayama University, Okayama, Japan., Ohta N; Section of Environmental Parasitology, Graduate School of Medical Dental Sciences, Tokyo Medical Dental University, Bunkyo-ku, Tokyo, Japan., Matsumoto Y; Laboratory of Molecular Immunology, Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Iwanaga S; Section of Environmental Parasitology, Graduate School of Medical Dental Sciences, Tokyo Medical Dental University, Bunkyo-ku, Tokyo, Japan.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2019 Mar 25; Vol. 13 (3), pp. e0007235. Date of Electronic Publication: 2019 Mar 25 (Print Publication: 2019).
DOI: 10.1371/journal.pntd.0007235
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje