Development of drug resistance in Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense.: Treatment of human African trypanosomiasis with natural products (Review)

Autoren

Efferth

DOI

10.3892/ijmm_00000037

ISSN

1107-3756

Ausgabe der Veröffentlichung

4

Zeitschrift

International Journal of Molecular Medicine

Datum der Veröffentlichung

1998

Status

Published

Herausgeber

Spandidos Publications

Herausgeber URL

http://dx.doi.org/10.3892/ijmm_00000037

Datum der Datenerfassung

2017

Titel

Development of drug resistance in Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Treatment of human African trypanosomiasis with natural products (Review)

Ausgabe der Zeitschrift

22

Data source: Crossref

Abstract

Human African trypanosomiasis is an infectious disease which has resulted in the deaths of thousands of people in Sub-Saharan Africa. Two subspecies of the protozoan parasite Trypanosoma brucei are the causative agents of the infection, whereby T. b. gambiense leads to chronic development of the disease and T. b. rhodesiense establishes an acute form, which is fatal within months or even weeks. Current chemotherapy treatment is complex, since special drugs have to be used for the different development stages of the disease, as well as for the parasite concerned. Melarsoprol is the only approved drug for effectively treating both subspecies of human African trypanosomiasis in its advanced stage, however, the drug's potency is constrained due to an unacceptable side effect: encephalopathy, which develops in one out of every 20 patients who are treated with the drug. In addition to the deleterious treatment with melarsoprol, the number of drug-resistant strains of T. brucei supp. increases. Mechanisms of drug resistance have been elucidated and involve decreased drug import through the loss of the purine transporter P2 as well as enhanced drug export, mediated by a multidrug resistance-associated protein called TbMRPA. Thereby, the medical treatment with the available chemotherapeutics becomes exceedingly difficult. A promising strategy for research into new drugs and moreover, to overcome drug resistance, are compounds derived from natural sources. This study provides an overview of the recently discovered small molecules with trypanocidal activity against T. b. gambiense and T. b. rhodesiense. In addition, former promising compounds are touched upon.

Addresses

Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.

Autoren

Stefanie Gehrig
Thomas Efferth

eISSN

1791-244X

Externe Identifier

PubMed Identifier: 18813846

Open access

false

ISSN

1107-3756

Ausgabe der Veröffentlichung

4

Zeitschrift

International journal of molecular medicine

Schlüsselwörter

Animals
Humans
Trypanosoma brucei gambiense
Trypanosoma brucei rhodesiense
Trypanosomiasis, African
Biological Products
Drug Resistance

Sprache

eng

Medium

Print

Paginierung

411 - 419

Datum der Veröffentlichung

2008

Status

Published

Datum der Datenerfassung

2008

Titel

Development of drug resistance in Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Treatment of human African trypanosomiasis with natural products (Review).

Sub types

Review
Journal Article

Ausgabe der Zeitschrift

22

Data source: Europe PubMed Central

Abstract

Human African trypanosomiasis is an infectious disease which has resulted in the deaths of thousands of people in Sub-Saharan Africa. Two subspecies of the protozoan parasite Trypanosoma brucei are the causative agents of the infection, whereby T. b. gambiense leads to chronic development of the disease and T. b. rhodesiense establishes an acute form, which is fatal within months or even weeks. Current chemotherapy treatment is complex, since special drugs have to be used for the different development stages of the disease, as well as for the parasite concerned. Melarsoprol is the only approved drug for effectively treating both subspecies of human African trypanosomiasis in its advanced stage, however, the drug's potency is constrained due to an unacceptable side effect: encephalopathy, which develops in one out of every 20 patients who are treated with the drug. In addition to the deleterious treatment with melarsoprol, the number of drug-resistant strains of T. brucei supp. increases. Mechanisms of drug resistance have been elucidated and involve decreased drug import through the loss of the purine transporter P2 as well as enhanced drug export, mediated by a multidrug resistance-associated protein called TbMRPA. Thereby, the medical treatment with the available chemotherapeutics becomes exceedingly difficult. A promising strategy for research into new drugs and moreover, to overcome drug resistance, are compounds derived from natural sources. This study provides an overview of the recently discovered small molecules with trypanocidal activity against T. b. gambiense and T. b. rhodesiense. In addition, former promising compounds are touched upon.

Autoren

Stefanie Gehrig
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/18813846

ISSN

1107-3756

Ausgabe der Veröffentlichung

4

Zeitschrift

Int J Mol Med

Schlüsselwörter

Animals
Biological Products
Drug Resistance
Humans
Trypanosoma brucei gambiense
Trypanosoma brucei rhodesiense
Trypanosomiasis, African

Sprache

eng

Country

Greece

Paginierung

411 - 419

Datum der Veröffentlichung

2008

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2008

Titel

Development of drug resistance in Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Treatment of human African trypanosomiasis with natural products (Review).

Sub types

Journal Article
Review

Ausgabe der Zeitschrift

22

Data source: PubMed

Development of drug resistance in Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense.: Treatment of human African trypanosomiasis with natural products (Review)

Tools