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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Antimalarial activity of isoquine against Kenyan Plasmodium falciparum clinical isolates and association with polymorphisms in pfcrt and pfmdr1 genes
Journal of Antimicrobial Chemotherapy, Volume 68, No. 4, Article dks471, Year 2013
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Description
Background: The use of amodiaquine in prophylaxis is associated with serious toxicity, resulting from its metabolic conversion into a reactive quinone-imine metabolite by the hepatic cytochrome P450. To circumvent this toxicity, several amodiaquine analogues that lack the potential to form a quinone-imine derivative, while retaining antimalarial activity, have been designed. Isoquine is one of these promising molecules that has already reached Phase I clinical trials in humans. Methods: We analysed the in vitro activity of isoquine against 62 Plasmodium falciparum isolates collected in Kenya and the association of this activity with polymorphisms in pfcrt and pfmdr1 genes. Results: The median concentration of isoquine that inhibited 50% of parasite growth (IC50) was 9 nM, compared with 56 nM chloroquine, 8 nM amodiaquine, 10 nM desethylamodiaquine, 69 nM lumefantrine and 1 nM dihydroartemisinin. Isoquine activity was correlated with polymorphisms in pfcrt at codon 76, but not in pfmdr1 at codon 86. Conclusions: The high activity of isoquine against field isolates, including chloroquine-resistant isolates, with IC50<10 nM, warrants its further development as an antimalarial. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Authors & Co-Authors
Okombo, John
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Kiara, Steven M.
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Abdirahman, Abdi
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Mwai, Leah
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Ohuma, Eric O.
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Borrmann, Steffen
Kenya, Nairobi
Wellcome Trust Research Laboratories Nairobi
Germany, Heidelberg
Medizinischen Fakultät Heidelberg
Nzila, Alexis M.
Saudi Arabia, Dhahran
King Fahd University of Petroleum and Minerals
Ward, Stephen Andrew
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Statistics
Citations: 8
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1093/jac/dks471
ISSN:
03057453
e-ISSN:
14602091
Research Areas
Cancer
Genetics And Genomics
Noncommunicable Diseases
Study Locations
Kenya