OBJECTIVES: To assess the activity of a new organometallic chloroquine analogue, ferroquine, against numerous Plasmodium falciparum isolates from Gabon. METHODS: The in vitro susceptibility of 116 P. falciparum isolates to chloroquine and ferroquine was assessed using the isotopic microtest. All isolates were from outpatients in the Franceville and Bakoumba medical centres in the province of Haut-Ogooué, south-east Gabon. RESULTS: The in vitro resistance to chloroquine was 51.8% in Franceville and 96.7% in Bakoumba. The IC50 geometric mean (95% CI) of ferroquine against isolates in Franceville was 16.0 (14.4-17.8) nM, with individual values ranging from 1.0 to 47.0 nM; in Bakoumba it was 27.9 (23.4-33.2) nM, with individual values ranging from 1.0 to 62.0 nM. Compared with chloroquine, ferroquine was 5.3 times more active on isolates susceptible to chloroquine, and 13.3 times more active on isolates resistant to chloroquine. A weak positive correlation was observed between responses of these two drugs, but too low to demonstrate cross-resistance. CONCLUSIONS: Ferroquine may be useful as an alternative drug for treating chloroquine-resistant malaria.
OBJECTIVES: To assess the activity of a new organometallic chloroquine analogue, ferroquine, against numerous Plasmodium falciparum isolates from Gabon. METHODS: The in vitro susceptibility of 116 P. falciparum isolates to chloroquine and ferroquine was assessed using the isotopic microtest. All isolates were from outpatients in the Franceville and Bakoumba medical centres in the province of Haut-Ogooué, south-east Gabon. RESULTS: The in vitro resistance to chloroquine was 51.8% in Franceville and 96.7% in Bakoumba. The IC50 geometric mean (95% CI) of ferroquine against isolates in Franceville was 16.0 (14.4-17.8) nM, with individual values ranging from 1.0 to 47.0 nM; in Bakoumba it was 27.9 (23.4-33.2) nM, with individual values ranging from 1.0 to 62.0 nM. Compared with chloroquine, ferroquine was 5.3 times more active on isolates susceptible to chloroquine, and 13.3 times more active on isolates resistant to chloroquine. A weak positive correlation was observed between responses of these two drugs, but too low to demonstrate cross-resistance. CONCLUSIONS:Ferroquine may be useful as an alternative drug for treating chloroquine-resistant malaria.
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Authors: Christian Supan; Ghyslain Mombo-Ngoma; Maryvonne Kombila; Carmen L Ospina Salazar; Jana Held; Bertrand Lell; Cathy Cantalloube; Elhadj Djeriou; Bernhards Ogutu; John Waitumbi; Nekoye Otsula; Duncan Apollo; Mark E Polhemus; Peter G Kremsner; Douglas S Walsh Journal: Am J Trop Med Hyg Date: 2017-07-19 Impact factor: 2.345
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