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...
Autores principales: | , , , , |
---|---|
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 |