Design and synthesis of small-molecule inhibitors as anti-malarial and anti-serpin agents

<p>This work describe the design, synthesis and evaluation of small-molecule inhibitors of two different biological targets: <em>Plasmodium falciparium</em>, the most virulent malarial parasite in humans, and plasminogen activator inhibitor-1 (PAI-1), an endogenous serine proteases inhibitor implicated in a wide range of biological processes. Malaria is one of the top global health threats, and there is a great need for developing effective new chemotherapies. PAI-1 is a major component in the regulation of the plasminogen activation system, and the overexpression of this protein has been implicated in a number of conditions, such as thrombosis, atherosclerosis, and myocardial infarction. The research discussed concerns the design and synthesis of enantiomerically pure anti-malarial compounds containing chiral 1,2-aminoalcohol moiety. In addition, the synthesis and biological evaluation of several highly potent, novel, polygalloyl PAI-1 inhibitors based on common carbohydrates and tethers of various lengths is also presented.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Open Access Thesis

Discipline thesis:degree_discipline

Chemistry

Year

2008

Author dc:creator

• Puscau, Maria Mirela

Contributors dc:contributor

• Cory Emal, PhD, Chair
• Harriet Lindsay, PhD
• Gregg Wilmes, PhD

• Antimalarials Research
• Antiparasitic agents
• Malaria Treatment
• Chemistry

Repository record dc:identifier

https://commons.emich.edu/theses/156

OAI identifier oai:identifier

oai:commons.emich.edu:theses-1155