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In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border

BACKGROUND: On the borders of Thailand, Plasmodium falciparum has become resistant to nearly all available drugs, and there is an urgent need to find new antimalarial drugs or drug combinations. Ferroquine (SSR97193) is a new 4-aminoquinoline antimalarial active against chloroquine resistant and sen...

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Autores principales: Barends, Marion, Jaidee, Anchalee, Khaohirun, Nopparat, Singhasivanon, Pratap, Nosten, François
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934364/
https://www.ncbi.nlm.nih.gov/pubmed/17597537
http://dx.doi.org/10.1186/1475-2875-6-81
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author Barends, Marion
Jaidee, Anchalee
Khaohirun, Nopparat
Singhasivanon, Pratap
Nosten, François
author_facet Barends, Marion
Jaidee, Anchalee
Khaohirun, Nopparat
Singhasivanon, Pratap
Nosten, François
author_sort Barends, Marion
collection PubMed
description BACKGROUND: On the borders of Thailand, Plasmodium falciparum has become resistant to nearly all available drugs, and there is an urgent need to find new antimalarial drugs or drug combinations. Ferroquine (SSR97193) is a new 4-aminoquinoline antimalarial active against chloroquine resistant and sensitive P. falciparum strains in vivo and in vitro. This antimalarial organic iron complex (a ferrocenyl group has been associated with chloroquine) is meant to use the affinity of Plasmodium for iron to increase the probability for encountering the anti-malarial molecule. The aim of the present study was to investigate the activity of ferroquine against P. falciparum isolates from an area with a known high multi-drug resistance rate. METHODS: Parasite isolates were obtained from patients with acute falciparum malaria attending the clinics of SMRU. In vitro cultures of these isolates were set-up in the SMRU-laboratory on pre-dosed drug plates, and grown in culture for 42 hours. Parasite growth was assessed by the double-site enzyme-linked pLDH immunodetection (DELI) assay. RESULTS: Sixty-five P. falciparum isolates were successfully grown in culture. The ferroquine mean IC(50 )(95% CI) was 9.3 nM (95% C.I.: 8.7 – 10.0). The mean IC50 value for the principal metabolite of ferroquin, SR97213A, was 37.0 nM (95% C.I.: 34.3 – 39.9), which is four times less active than ferroquine. The isolates in this study were highly multi-drug resistant but ferroquine was more active than chloroquine, quinine, mefloquine and piperaquine. Only artesunate was more active than ferroquine. Weak but significant correlations were found between ferroquine and its principal metabolite (r(2 )= 0.4288), chloroquine (r(2 )= 0.1107) and lumefantrine (r(2 )= 0.2364). CONCLUSION: The results presented in this study demonstrate that the new ferroquine compound SSR97193 has high anti-malarial activity in vitro against multi-drug resistant P. falciparum.
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spelling pubmed-19343642007-07-28 In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border Barends, Marion Jaidee, Anchalee Khaohirun, Nopparat Singhasivanon, Pratap Nosten, François Malar J Case Study BACKGROUND: On the borders of Thailand, Plasmodium falciparum has become resistant to nearly all available drugs, and there is an urgent need to find new antimalarial drugs or drug combinations. Ferroquine (SSR97193) is a new 4-aminoquinoline antimalarial active against chloroquine resistant and sensitive P. falciparum strains in vivo and in vitro. This antimalarial organic iron complex (a ferrocenyl group has been associated with chloroquine) is meant to use the affinity of Plasmodium for iron to increase the probability for encountering the anti-malarial molecule. The aim of the present study was to investigate the activity of ferroquine against P. falciparum isolates from an area with a known high multi-drug resistance rate. METHODS: Parasite isolates were obtained from patients with acute falciparum malaria attending the clinics of SMRU. In vitro cultures of these isolates were set-up in the SMRU-laboratory on pre-dosed drug plates, and grown in culture for 42 hours. Parasite growth was assessed by the double-site enzyme-linked pLDH immunodetection (DELI) assay. RESULTS: Sixty-five P. falciparum isolates were successfully grown in culture. The ferroquine mean IC(50 )(95% CI) was 9.3 nM (95% C.I.: 8.7 – 10.0). The mean IC50 value for the principal metabolite of ferroquin, SR97213A, was 37.0 nM (95% C.I.: 34.3 – 39.9), which is four times less active than ferroquine. The isolates in this study were highly multi-drug resistant but ferroquine was more active than chloroquine, quinine, mefloquine and piperaquine. Only artesunate was more active than ferroquine. Weak but significant correlations were found between ferroquine and its principal metabolite (r(2 )= 0.4288), chloroquine (r(2 )= 0.1107) and lumefantrine (r(2 )= 0.2364). CONCLUSION: The results presented in this study demonstrate that the new ferroquine compound SSR97193 has high anti-malarial activity in vitro against multi-drug resistant P. falciparum. BioMed Central 2007-06-27 /pmc/articles/PMC1934364/ /pubmed/17597537 http://dx.doi.org/10.1186/1475-2875-6-81 Text en Copyright © 2007 Barends 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 Case Study
Barends, Marion
Jaidee, Anchalee
Khaohirun, Nopparat
Singhasivanon, Pratap
Nosten, François
In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border
title In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border
title_full In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border
title_fullStr In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border
title_full_unstemmed In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border
title_short In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border
title_sort in vitro activity of ferroquine (ssr 97193) against plasmodium falciparum isolates from the thai-burmese border
topic Case Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934364/
https://www.ncbi.nlm.nih.gov/pubmed/17597537
http://dx.doi.org/10.1186/1475-2875-6-81
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