Novel 5’ Methylthioadenosine Nucleosidase Inhibitors Synergize Metronidazole Anti-Giardial Activity.

Abstract

Giardia intestinalis is a protozoan parasite responsible for giardiasis - a severe diarrheal disease which affects up to 33% of people in developing countries. Due to the recent emergence of metronidazole resistance, new anti-parasitic drugs are needed. One potential drug target is 5’ Methylthioadenosine Nucleosidase (MTN). MTN is required for purine and methionine salvage in pathways in the parasite. MTN inhibition would impair cell viability by starving the parasite for these essential nutrients. In this study, non-nucleoside MTN inhibitors were tested in vitro for their ability to synergize the anti-giardial activity of metronidazole.

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Novel 5’ Methylthioadenosine Nucleosidase Inhibitors Synergize Metronidazole Anti-Giardial Activity.

Giardia intestinalis is a protozoan parasite responsible for giardiasis - a severe diarrheal disease which affects up to 33% of people in developing countries. Due to the recent emergence of metronidazole resistance, new anti-parasitic drugs are needed. One potential drug target is 5’ Methylthioadenosine Nucleosidase (MTN). MTN is required for purine and methionine salvage in pathways in the parasite. MTN inhibition would impair cell viability by starving the parasite for these essential nutrients. In this study, non-nucleoside MTN inhibitors were tested in vitro for their ability to synergize the anti-giardial activity of metronidazole.