Computational and experimental analysis identified 6-diazo-5-oxonorleucine as a potential agent for treating infection by Plasmodium falciparum

Kitiporn, Plaimas and Wang, Yulin and Rotimi, S. O and Olasehinde, G. I and Fatumo, Segun and Lanzer, Michael and Adebiyi, Ezekiel and Konig, R. (2013) Computational and experimental analysis identified 6-diazo-5-oxonorleucine as a potential agent for treating infection by Plasmodium falciparum. Infection, Genetics and Evolution, 20. pp. 389-395.

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Abstract

Plasmodium falciparum (PF) is the most severe malaria parasite. It is developing resistance quickly to existing drugs making it indispensable to discover new drugs. Effective drugs have been discovered targeting metabolic enzymes of the parasite. In order to predict new drug targets, computational methods can be used employing database information of metabolism. Using this data, we performed recently a computational network analysis of metabolism of PF. We analyzed the topology of the network to find reactions which are sensitive against perturbations, i.e., when a single enzyme is blocked by drugs. We now used a refined network comprising also the host enzymes which led to a refined set of the five targets glutamyl–tRNA (gln) amidotransferase, hydroxyethylthiazole kinase, deoxyribose–phophate aldolase, pseudouridylate synthase, and deoxyhypusine synthase. It was shown elsewhere that glutamyl– tRNA (gln) amidotransferase of other microorganisms can be inhibited by 6-diazo-5-oxonorleucine. Performing a half maximal inhibitory concentration (IC50) assay, we showed, that 6-diazo-5-oxonorleucine is also severely affecting viability of PF in blood plasma of the human host. We confirmed this by an in vivo study observing Plasmodium berghei infected mice.

Item Type:	Article
Subjects:	Q Science > Q Science (General)
Divisions:	Faculty of Medicine, Health and Life Sciences > School of Biological Sciences
Depositing User:	Mrs Patricia Nwokealisi
Date Deposited:	27 Jan 2014 12:06
Last Modified:	27 Jan 2014 12:06
URI:	http://eprints.covenantuniversity.edu.ng/id/eprint/2080

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