Title
A non-radiolabelled ferriprotoporphyrin IX biomineralisation inhibition test for the high throughput screening of antimalarial compounds
Date Issued
01 April 2002
Access level
metadata only access
Resource Type
journal article
Author(s)
Deharo E.
García R.N.
Oporto P.
Gimenez A.
Jullian V.
Ginsburg H.
Université Paul Sabatier
Abstract
Intraerythrocytic malaria parasites produce large amounts of toxic ferriprotoporphyrin IX (FP) during their digestion of host cell haemoglobin. The inhibition of biomineralisation of FP to haemozoin (or β-haematin) by antimalarial drugs underlies their mode of action. We have developed an in vitro microassay for testing the inhibition of biomineralisation by drugs. It is based on the detection by optical density measurement of solubilised β-haematin remaining after contact with drugs. The assay uses a 192-μM haemin chloride solution in dimethyl sulfoxide, 96-well filtration microplates as well as normal microplates; it lasts 18-24h and requires a spectrophotometer. We determined by this assay the IC50 of chloroquine phosphate (28 μM) and quinine base (324 μM) and showed that unlike previous methods it is insensitive to inorganic anions. We also determined the activity of synthetic dyes and plant extract to determinate the interference of coloured compounds on the accuracy of the test. We found that methylene blue, thionine (IC50 38 and 87 μM, respectively), and an extract of plants that contains quinoline derivatives, inhibited the biomineralisation of FP regardless of their intrinsic colour. © 2002 Elsevier Science (USA). All rights reserved.
Start page
252
End page
256
Volume
100
Issue
4
Language
English
OCDE Knowledge area
Química orgánica Farmacología, Farmacia
Scopus EID
2-s2.0-0036557772
PubMed ID
Source
Experimental Parasitology
ISSN of the container
00144894
DOI of the container
10.1016/S0014-4894(02)00027-9
Source funding
Organization of American States
Institut de Recherche pour le Développement
Sponsor(s)
The project was funded by the Institut de Recherche pour le Développement (France), and the Organisacion de los Estados Americanos (OEA) proyecto Flora Regional.
Sources of information: Directorio de Producción Científica Scopus