In Vitro Activity of Ferroquine (SSR 97193) Against Plasmodium Falciparum Isolates from the Thai-Burmese Border

Overview

Journal Malar J

Publisher Biomed Central

Specialty Tropical Medicine

Date 2007 Jun 29

PMID 17597537

Citations 28

Authors

Marion Barends

Anchalee Jaidee

Nopparat Khaohirun

Pratap Singhasivanon

Francois Nosten

Affiliations

Soon will be listed here.

Abstract

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 IC50 (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 (r2 = 0.4288), chloroquine (r2 = 0.1107) and lumefantrine (r2 = 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.

Citing Articles

Investigations on the Novel Antimalarial Ferroquine in Biomimetic Solutions Using Deep UV Resonance Raman Spectroscopy and Density Functional Theory.

Domes R, Frosch T Anal Chem. 2023; 95(19):7630-7639.

PMID: 37141178 PMC: 10193365. DOI: 10.1021/acs.analchem.3c00539.

Rosetting Responses of Plasmodium-infected Erythrocytes to Antimalarials.

Lee W, Russell B, Lau Y, Nosten F, Renia L Am J Trop Med Hyg. 2022; .

PMID: 35405642 PMC: 9209907. DOI: 10.4269/ajtmh.21-1229.

Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity.

Aguiar A, Murce E, Cortopassi W, Pimentel A, Almeida M, Barros D Int J Parasitol Drugs Drug Resist. 2018; 8(3):459-464.

PMID: 30396013 PMC: 6215995. DOI: 10.1016/j.ijpddr.2018.10.002.

Tackling resistance: emerging antimalarials and new parasite targets in the era of elimination.

Mathews E, Odom John A F1000Res. 2018; 7.

PMID: 30135714 PMC: 6073090. DOI: 10.12688/f1000research.14874.1.

Quinoline-Based Hybrid Compounds with Antimalarial Activity.

Nqoro X, Tobeka N, Aderibigbe B Molecules. 2017; 22(12).

PMID: 29257067 PMC: 6149725. DOI: 10.3390/molecules22122268.

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