Medicinal and Pharmaceutical Chemistry Commons^™

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Psychoactive Synthetic Cathinones (Or 'Bath Salts'): Investigation Of Mechanisms Of Action, Farhana Sakloth

Theses and Dissertations

Synthetic cathinones represent threatening and high abuse-potential designer drugs. These are analogs of cathinone (the b-keto analog of amphetamine (AMPH)) a naturally occurring stimulant found in the plant Catha Edulis. Methcathinone (MCAT) was the first synthetic analog of cathinone to be identified in 1987 by Glennon and co-workers and it exerted its action primarily through the dopamine transporter (DAT). Most central stimulants exert their action via monomaine transporters by causing either the release (e.g. cathinone analogs such as MCAT) or by preventing the reuptake (e.g. cocaine) of the neurotransmitter dopamine (DA) thus increasing the extracellular synaptosomal concentration of this …

An Analysis Of The Cause, Effect & Control Of Hyperlipidemia From A Nursing Perspective, Melissa Rodgers

Theses and Dissertations

Two of the top four causes of death worldwide, heart disease and stroke, are related to hyperlipidemia, elevated cholesterol levels; these two illnesses account for approximately seventeen million deaths each year (World Health Organization, 2014). In order to combat the prevalence of these illnesses, the National Cholesterol Educational Panel has issued guidelines regarding cholesterol management. Extensive research has been published concerning cholesterol management. However, a gap remains between evidenced-based practice and community awareness of this phenomenon. This manuscript compiles research from peer reviewed nursing journals and acclaimed government and national organizations to express the cause, effect, and control of hyperlipidemia …

Hydropathic Interactions And Protein Structure: Utilizing The Hint Force Field In Structure Prediction And Protein‐Protein Docking., Mostafa H. Ahmed

Theses and Dissertations

Protein structure predication is a field of computational molecular modeling with an enormous potential for improvement. Side-chain geometry prediction is a critical component of this process that is crucial for computational protein structure predication as well as crystallographers in refining experimentally determined protein crystal structures. The cornerstone of side-chain geometry prediction are side-chain rotamer libraries, usually obtained through exhaustive statistical analysis of existing protein structures. Little is known, however, about the driving forces leading to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines extracted from the PDB reveals their …

Development Of Bivalent Ligands Targeting The Putative Ccr5-Mor Heterodimer, Thomas Raborg

Theses and Dissertations

Chemokine receptor CCR5 (CCR5) is a G-protein coupled receptor (GPCR) predominantly expressed on leukocytes, or white blood cells.1–3 During inflammation, the body releases chemokines that bind to receptors such as CCR5 and attract leukocytes to the area of inflammation, leading to an immunological response.1 CCR5 is also an important receptor in the human immunodeficiency virus's (HIV-1) invasion of host cells, as CCR5 acts as a co-receptor that facilitates HIV-1 viral entry.4,5 The continued destruction of leukocytes as a result of HIV-1 viral entry produces a disease state called acquired immunodeficiency syndrome (AIDS).5 Of note, this receptor is also expressed on …

Synthesis Of Mesoionic Nucleosides As Potential Antineoplastic Agents, Shanaz Mohammedali Tejani

Theses and Dissertations

During the past few decades, analogs of purine nucleosides have been described that are modified either in the heterocyclic base, sugar moiety or both, and many of these modified nucleosides display antiviral and/or antineoplastic activity. The Class II mesoionic purinones are isosteric with their non~mesoionic purinone counterparts. It is conceivable that the mesoionic purinone nucleosides might constitute an entirely novel class of modified nucleosides with potential chemotherapeutic activity. That the mesoionic heterobases are bioisosteric as well as isosteric with non-mesoionic purinones was realized by demonstrating that certain mesoionic xanthine derivatives, such as Anhydro-8-ethylw-5-hydroxy-7-oxo-l,3,4-thiadiazolo[3,2-a]pyrimidinium hydroxide and Anhydro-6-p-chlorobenzyl-8-ethyl-5-hydroxy-7-oxo—l,3,4—thiadiazolo [3,2-a]pyrimidinium hydroxide were comparable …

Synthesis And Biological Evaluation Of Sparsomycin Analogues, Scherer Preston Sanders

Theses and Dissertations

In 1962, Owen, Dietz, and Camiener reported the isolation of a new antitumor antibiotic from the culture filtrate of Streptomyces sparsogenes. The structure of the crystalline antibiotic, named sparsomycin, remained elusive until 1970, when Wiley and MacKellar reported results of spectroscopic and degradation studies which elucidated the structure. In addition to the molecular structure, investigators have examined the mechanism of action, toxicity, and related analogues, striving to establish sparsomycin or a synthetic analogue's usefulness as an effective chemotherapeutic agent.

The initial pharmacological evaluation of sparsomycin revealed it possessed activity against KB human epidermoid carcinoma cells, a variety of gram-negative and …

Synthesis And Evaluation Of Some Arylalkenyl And Arylepoxyalkyl Hydrogen Succinates And Hydrogen Glutarates As Inhibitors Of Rat Liver Β-Hydroxy-Β-Methylglutaryl Coenzyme A Reductase, Paul Emil Marecki

Theses and Dissertations

Atherosclerotic disease is an almost universal phenomenon and increases in severity and frequency with increasing age. Atherosclerosis may contribute to several disorders including bursting of an artery, blockage of an artery, or induction of arterial clotting. The culmination of these diseases is usually premature since at the time of death the unaffected organs are in reasonably satisfactory condition and could have operated for several more years. Among the many factors which act in concert to produce the disease, serum cholesterol levels play a central role. It has been suggested that the lowering of cholesterol levels will provide an effective means …