Drug discovery against malaria parasite: drug repositioning strategy

Malaria, caused by Plasmodium spp., causes ~1 million deaths each year and there are ever present problems due to drug resistance. In this work, I used drug-repositioning strategy with bisphosphonates to discover a lead that is active against malaria in vivo. The developmental procedures include, in vitro high throughput screening, x-ray crystallography and other biophysical techniques. First, a computational method was developed to elucidate the target of bisphosphonate in malaria parasite and, second, inhouse synthesized library of prenyl synthase inhibitors was used to find the lead, an analog of zoledronate, against the parasite, which the x-ray structure bound to target enzyme, farnesyl diphosphate synthase (FPPS), was solved. Also, the effect of lipophilic bisphosphonate against liver stage malaria parasite was investigated. Lastly, I studied the mechanism and inhibition of IspH, the last enzyme of nonmevalonate pathway, for discovery of a novel target for infectious disease.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics & Computnl Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• No, Joo Hwan

Contributors dc:contributor

• Oldfield, Eric
• Gennis, Robert B.
• Baranger, Anne M.
• Mitchell, Douglas A.

• Drug discovery
• Malaria

Statement dc:rights

• Copyright 2011 Joo Hwan No

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/26307

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/26307