A fluorescence-based assay for the uptake of CPD0801 (DB829) by African trypanosomes

Molecular and Biochemical Parasitology
Christopher P WardHarry P de Koning

Abstract

Drug therapies currently used for second stage Human African Trypanosomiasis (HAT) exhibit problems with toxicity, difficulty of administration, and resistance linked to the loss of transporter function. Key to the development of new drugs for HAT is a better understanding of the transport properties of candidate compounds. Standard methods for studying transport utilize radio-labelled permeant or HPLC-MS, however the natural fluorescence of many trypanocidal compounds can be exploited. Here we present a fluorescence-based assay for measuring uptake, by trypanosomes, of CPD0801, a drug candidate for second stage HAT. Sample fluorescence is measured in a 96-well format using a benchtop fluorimeter. Our method is directly applicable to the study of other diamidines with similar fluorescent properties and readily adapted for use with other cell types or fluorescent molecules as we demonstrate for the veterinary trypanocide ethidium.

References

Jul 1, 1982·Molecular and Biochemical Parasitology·P BorstJ James
May 24, 2003·Trends in Parasitology·Patrick G BrayHarry P de Koning
Jul 26, 2005·FEMS Microbiology Reviews·Harry P de KoningRichard J S Burchmore
May 26, 2006·Antimicrobial Agents and Chemotherapy·Amanda M MathisJames Edwin Hall
Aug 17, 2006·Molecular Pharmacology·Charlotte A LanteriMichael P Barrett
Aug 30, 2008·Annals of Neurology·Peter G E Kennedy
Oct 25, 2008·Transactions of the Royal Society of Tropical Medicine and Hygiene·Manica BalasegaramFrancesco Checchi

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African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.