Generation of novel small molecules as inhibitors of plasminogen activator inhibitor-1

<p>Plasminogen activator inhibitor (PAI-1) is a member of the serine protease inhibitor (serpin) family of proteins, which inhibits certain serine proteases, such as tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and thus is a primary regulator of fibrinolysis, the process that results in breakdown of blood clots. PAI-1 also exhibits effects on various human ailments including atherosclerosis, stroke and diabetes, with which high levels of PAI-1 have been associated. The goal of this research study is to design novel, potent, and specific small molecule inhibitors of PAI-1. The structural intricacy of the PAI-1 allows for multiple prospective binding sites. This research study explores the synthesis and screening of biological activity of various structural analogues of the lead molecule I-26, which was identified through high-throughput screening. It was hypothesized that the structural alterations of the lead molecule would affect the potency of PAI-1 inhibitor. The design rationale, synthesis and structure-activity relationships of novel small molecule inhibitors of PAI-1 are discussed.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Campus Only Thesis

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2013

Author dc:creator

• Guntaka, Naga Sandhya

Contributors dc:contributor

• Cory Emal, PhD, Chair
• Harriet Lindsay, PhD
• Deborah Heyl-Clegg, PhD

• fibrinolysis
• molecules
• plasminogen
• Chemistry

Repository record dc:identifier

https://commons.emich.edu/theses/622

OAI identifier oai:identifier

oai:commons.emich.edu:theses-2001