Medicinal Chemistry Dissertations and Theses: Recent submissions
Now showing items 41-60 of 80
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Investigation of Natural Product Scaffolds for the Development of Opioid Receptor Ligands
(University of Kansas, 2012-08-31)Kappa opioid (KOP) receptors have been suggested as an alternative target to the mu opioid (MOP) receptor for the treatment of pain because KOP activation is associated with fewer negative side-effects (respiratory depression, ... -
Phase-Trafficking Methods in Natural Products, Modulators of Organic Anion Transporting Polypeptides from Rollinia emarginata, and Pregnane and Cardiac Glycosides from Asclepias spp.
(University of Kansas, 2012-05-31)For decades, chemists and medicinal chemists have found in nature the source of inspiration for drug discovery and development. This work describes several aspects of the interaction between the fields of natural products ... -
Synthetic Strategies for the Lepadiformines and Cylindricine C via Tandem Schmidt Reactions
(University of Kansas, 2011-12-31)Marine flora and fauna have provided numerous alluring natural products, some of which contribute to treating diseases. The genus Clavelina is the source of a variety of tricyclic alkaloids, including the lepadiformine and ... -
A New Generation of Hsp90 Inhibitors: Addressing Isoform Selectivity and Heat Shock Induction
(University of Kansas, 2011-12-31)The 90 kDa heat shock proteins (Hsp90) are molecular chaperones that are upregulated in response to cellular stress and are responsible for the conformational maturation, activation and/or stability of more than 200 client ... -
The Pursuit of Unshocking Hsp90 Inhibitors: Development of Gedunin and Cruentaren A as Chemical Leads
(University of Kansas, 2011-12-31)Abstract: The 90 kDa heat shock protein (Hsp90) is a molecular chaperone that is critical cellular survival and growth under both typical and stressful conditions. Hsp90 is responsible for the maturation and stability of ... -
Development of libraries inspired by sparteine
(University of Kansas, 2011-21-31)This thesis describes the development of libraries inspired by the natural product sparteine. Multi-gram synthesis of important intermediate representing sparteine core has been carried out. A scalable process has been ... -
ANTI-PROLIFERATIVE WITHANOLIDES FROM VASSOBIA BREVIFLORA AND WITHANIA SOMNIFERA
(University of Kansas, 2011-08-31)In order to identify anti-proliferative compounds from selected Latin American plants, approximately 200 plant extracts were screened by the MTS assay (3-[4,5-dimethylthiazol-2yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H ... -
Modulators of Toll-like Receptors -7 and -8
(University of Kansas, 2011-05-31)Toll-like receptors (TLR)-7/-8 are innate immune receptors present in the endosomal compartment that are activated by single-stranded RNA (ssRNA) molecules of viral as well as nonviral origin, inducing the production of ... -
Diverse Applications of Flow Technology in Discovery Chemistry
(University of Kansas, 2011-08-31)The research presented herein describes the development of methods and applications of flow technology in discovery chemistry. The first two chapters highlight the use of several beneficial features offered by flow technology ... -
The Synthesis and Pharmacological Evaluation of Salvinorin A Analogues as Opioid Receptor Probes
(University of Kansas, 2011-08-31)Kappa opioid (KOP) receptors have been shown to be involved in the control of several abuse related effects of central nervous system stimulants. KOP receptor agonists have been shown to modulate the activity of dopamine ... -
Improving the Yeast Three-Hybrid System for High-Throughput Target Discovery
(University of Kansas, 2011-05-27)High-throughput screening and rational design can be used to create bioactive compounds with high affinity for selected therapeutic targets. However, a significant challenge in preclinical drug development is the identification ... -
Design, Synthesis, and Evaluation of Site-Specific Hsp90 Inhibitors
(University of Kansas, 2011-06-13)The heat shock protein 90 (Hsp90) family of molecular chaperones is responsible for the conformational maturation of nascent polypeptides and refolding of denatured proteins. Hsp90 is known to play an important role in the ... -
Design, Synthesis and Evaluation of Non-Canonical Hsp90 Modulators
(University of Kansas, 2011-03-18)Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at ~700 &muM in breast cancer cells (SKBr3). Although ... -
A TALE OF TWO ENZYMES: IDENTIFICATION OF AN UNKNOWN LIGAND BOUND TO CYTOCHROME P450 2A13 AND UNDERSTANDING SUBSTRATE SELECTIVITY OF CYTOCHROME P450 2E1
(University of Kansas, 2009-04-09)Cytochrome P450 (CYP) is the predominate superfamily of enzymes responsible for Phase I metabolism of drugs and other xenobiotics. Understanding the structural reasons for the substrate selectivity of these enzymes is ... -
A Small Molecule Modulator of Hsp90 Improves Experimental Diabetic Neuropathy
(University of Kansas, 2010-07-30)Background: Current Hsp90 inhibitors are therapeutically problematic. Although they induce a pro-survival heat shock response that promotes the refolding of damaged proteins, a confounding issue is that at these concentrations ... -
The Design, Synthesis and Evaluation of Peptide Ligands to Study Opioid Receptors
(University of Kansas, 2010-07-23)The δ opioid receptor (DOR) is involved in the modulation of μ opioid receptor (MOR) agonist mediated side effects such as the development of tolerance, and MOR and DOR may interact to form heterodimers capable of unique ... -
Modulators of Toll-like Receptors-4 and -2
(University of Kansas, 2009-08-31)The toxicity of Gram-negative bacterial endotoxin (lipopolysaccharide, LPS) resides in its structurally highly conserved glycolipid component called lipid A. The major goal of the first project was to further explore ... -
Synthesis and Evaluation of Novel Iminosugars as Potential Male Contraceptive Agents; and the Chemistry of 2,3-Dihydropyridin-4-(1H)-ones and Related Enaminones in Multicomponent Reactions
(University of Kansas, 2010-04-26)The iminosugar N-butyl-1-deoxynojirimycin (nB-DNJ) has reversible, nonhormonal contraceptive effects on C57B/L6 mice at micromolar concentrations. In order to increase the potency and bioavailability of this lead compound, ... -
Phenanthropiperidine Alkaloids: Methodology Development, Synthesis and Biological Evaluation
(University of Kansas, 2010-04-08)This work is directed towards the development of safe phenanthropiperidines for the treatment of cancer. It focuses on synthetic methodologies that facilitate their preparation and biological studies to better understand ... -
Part I. Approaches Toward the Total Synthesis of Tyloindicine F; Part II. Palladium-Catalyzed C−H Functionalization of β-enaminones
(University of Kansas, 2010-02-26)Tyloindicine F is a potent anticancer natural product first isolated from the Himalaya region of India. It demonstrated a unique profile in the NCI60 human tumor cell line anticancer drug screen. Due to its scarcity from ...