Cargando…

Antimalarial activity of a cis-terpenone

BACKGROUND: Malaria is the third most prevalent cause of infectious disease in the world. Resistance of the parasite to classical drugs makes the discovery of new and effective drugs more urgent. The oxidized derivative of hydroxy-cis terpenone (OHCT) is a synthetic molecule that is not toxic to cul...

Descripción completa

Detalles Bibliográficos
Autores principales: Mayer, DC Ghislaine, Bruce, Maimuna, Kochurova, Olga, Stewart, Jennifer K, Zhou, Qibing
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711970/
https://www.ncbi.nlm.nih.gov/pubmed/19555505
http://dx.doi.org/10.1186/1475-2875-8-139
_version_ 1782169469854941184
author Mayer, DC Ghislaine
Bruce, Maimuna
Kochurova, Olga
Stewart, Jennifer K
Zhou, Qibing
author_facet Mayer, DC Ghislaine
Bruce, Maimuna
Kochurova, Olga
Stewart, Jennifer K
Zhou, Qibing
author_sort Mayer, DC Ghislaine
collection PubMed
description BACKGROUND: Malaria is the third most prevalent cause of infectious disease in the world. Resistance of the parasite to classical drugs makes the discovery of new and effective drugs more urgent. The oxidized derivative of hydroxy-cis terpenone (OHCT) is a synthetic molecule that is not toxic to cultured human liver cells at concentrations as high as 60 μM and inhibits activity of cytochrome P450s that metabolize many drugs. METHODS: OHCT activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum, and a P. falciparum clone that is partially resistant to artemisinin was assayed in vitro. RESULTS: OHCT at nanomolar concentrations was effective against all intraerythrocytic stages of P. falciparum and exhibited activity in vitro against both chloroquine-sensitive and -resistant strains of P. falciparum as well as a P. falciparum clone that is partially resistant to artemisinin. Moreover, OHCT exhibited potent activity against gametocytes, the form that is transmitted by mosquitoes and essential for the spread of malaria. CONCLUSION: OHCT displays strong growth inhibitory activity against all stages of P. falciparum and no evidence of toxicity to human cells in culture. It is easily synthesized and has the potential for inhibiting metabolism of drugs used in combination therapies.
format Text
id pubmed-2711970
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-27119702009-07-17 Antimalarial activity of a cis-terpenone Mayer, DC Ghislaine Bruce, Maimuna Kochurova, Olga Stewart, Jennifer K Zhou, Qibing Malar J Research BACKGROUND: Malaria is the third most prevalent cause of infectious disease in the world. Resistance of the parasite to classical drugs makes the discovery of new and effective drugs more urgent. The oxidized derivative of hydroxy-cis terpenone (OHCT) is a synthetic molecule that is not toxic to cultured human liver cells at concentrations as high as 60 μM and inhibits activity of cytochrome P450s that metabolize many drugs. METHODS: OHCT activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum, and a P. falciparum clone that is partially resistant to artemisinin was assayed in vitro. RESULTS: OHCT at nanomolar concentrations was effective against all intraerythrocytic stages of P. falciparum and exhibited activity in vitro against both chloroquine-sensitive and -resistant strains of P. falciparum as well as a P. falciparum clone that is partially resistant to artemisinin. Moreover, OHCT exhibited potent activity against gametocytes, the form that is transmitted by mosquitoes and essential for the spread of malaria. CONCLUSION: OHCT displays strong growth inhibitory activity against all stages of P. falciparum and no evidence of toxicity to human cells in culture. It is easily synthesized and has the potential for inhibiting metabolism of drugs used in combination therapies. BioMed Central 2009-06-25 /pmc/articles/PMC2711970/ /pubmed/19555505 http://dx.doi.org/10.1186/1475-2875-8-139 Text en Copyright © 2009 Mayer et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Mayer, DC Ghislaine
Bruce, Maimuna
Kochurova, Olga
Stewart, Jennifer K
Zhou, Qibing
Antimalarial activity of a cis-terpenone
title Antimalarial activity of a cis-terpenone
title_full Antimalarial activity of a cis-terpenone
title_fullStr Antimalarial activity of a cis-terpenone
title_full_unstemmed Antimalarial activity of a cis-terpenone
title_short Antimalarial activity of a cis-terpenone
title_sort antimalarial activity of a cis-terpenone
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711970/
https://www.ncbi.nlm.nih.gov/pubmed/19555505
http://dx.doi.org/10.1186/1475-2875-8-139
work_keys_str_mv AT mayerdcghislaine antimalarialactivityofacisterpenone
AT brucemaimuna antimalarialactivityofacisterpenone
AT kochurovaolga antimalarialactivityofacisterpenone
AT stewartjenniferk antimalarialactivityofacisterpenone
AT zhouqibing antimalarialactivityofacisterpenone