Date Approved
7-12-2013
Date Posted
1-14-2016
Degree Type
Campus Only Thesis
Degree Name
Master of Science (MS)
Department or School
Chemistry
Committee Member
Cory Emal, PhD, Chair
Committee Member
Harriet Lindsay, PhD
Committee Member
Deborah Heyl-Clegg, PhD
Abstract
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.
Recommended Citation
Guntaka, Naga Sandhya, "Generation of novel small molecules as inhibitors of plasminogen activator inhibitor-1" (2013). Master's Theses and Doctoral Dissertations. 622.
https://commons.emich.edu/theses/622