Organic Chemicals Commons^™

Synthesis And Biological Study Of Adenylyl Cyclase Inhibitors, Siyuan Sun, Zhishi Ye, Mingji Dai

The Summer Undergraduate Research Fellowship (SURF) Symposium

Adenylyl cyclases (AC) is a critical family of enzymes which modulates the dynamic cellular level of cAMP, cyclic adenosine monophosphate. The study of cAMP showed that it is indispensable for the signal transduction cascades during many physiological processes, such as immune responses and metabolism which highly relate to cancers. Previous studies of AC inhibitors have been limited due to a lack of isoform-selective small molecule modulators. Selectivity of the molecules is imperative to the activation of only the desired AC inhibitor. The design of the described project was to test the structure activity relationship (SAR) by synthesizing a class of …

Uhplc-Ms/Ms Analysis Of Arachidonic Acid And 10 Of Its Major Cytochrome P450 Metabolites As Free Acids In Rat Livers: Effects Of Hepatic Ischemia, Vindhya Edpuganti, Reza Mehvar

Pharmacy Faculty Articles and Research

The cytochrome P450 metabolites of arachidonic acid (AA) are mostly present in tissues, such as the liver, as bound to phospholipids, with only a small fraction available as free acids. The purpose of this study was to develop and validate a UHPLC-MS/MS method for quantitation of free liver concentrations of AA and four epoxygenated (5,6-, 8,9-, 11,12-, and 14,15-EET), four dihydroxylated (5,6-, 8,9-, 11,12-, and 14,15-DHET), and two ω/(ω-1) hydroxylated (19- and 20- HETEs) metabolites of AA in rat livers using deuterated internal standards. The analytes were rapidly and efficiently (79-92%) recovered from 100 mg of fresh liver into methanol. …

Endothelial And Smooth Muscle-Dependent Vascular Reactivity In Immature Arterialized Collateral Capillaries, Caitlin Koeroghlian

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) occurs due to the build up of atherosclerotic plaque and reduces blood flow to cause chronic ischemia. Patients with PAOD may experience intermittent claudication, or the pain in limb skeletal muscles due to a decease in blood flow. Collateral arteries can act as a natural bypass and improve blood flow to hypoxic tissue by creating an alternate route for blood to flow, but not all patients with PAOD have pre-existing collateral networks. Animal studies indicate that tissues without pre-existing collateral networks can form de novo collaterals from capillaries following occlusion of a feed artery. Unfortunately, …

Design, Synthesis And Biological Evaluation Of Novel Compounds With Cns-Activity Targeting Cannabinoid And Biogenic Amine Receptors, Alexander M. Sherwood

LSU New Orleans Theses and Dissertations

This work seeks to contribute to the discipline of neuropharmacology by way of structure activity relationship from the standpoint of an organic chemist. More specifically, we sought to develop robust synthetic methodology able to efficiently produce an array of compounds for the purpose of systematic evaluation of their interaction with specific sights within the central nervous system (CNS) in order to better understand the mind and to develop drugs that may have beneficial effects on neurological function.

The focus of these studies has been toward the development of novel molecules, using a structure-activity relationship approach, that exhibit binding affinity at …

Polyethylene Glycol Containing Rompolymers For The Modification Of Neuro-Protective Hemoglobin, Andrea L. Mccollum

Honors College Theses

Polyethylene glycol (PEG) has shown the ability to improve compatibility when used in combination with cell-free hemoglobin in the treatment of traumatic brain injuries. It has been demonstrated that the covalently bonded PEG increases the hydrodynamic radius of the hemoglobin and hence generates a physical barrier while slowing down the oxygen delivery of the strongly oxidative hemoglobin. In this context, I have been working on the development of synthetic pathways to incorporate PEG into monomers and polymers through both direct modification of (7-oxa)norbornene derivatives and post polymerization modification. Starting from the (7-oxa)norbornene anhydride derivatives, we have developed pathways to cationic …

Roles Of Dopamine Receptor On Chemosensory And Mechanosensory Primary Cilia In Renal Epithelial Cells, Viralkumar S. Upadhyay, Brian S. Muntean, Samred H. Kathem, Jangyoun J. Hwang, Wissam A. Aboualaiwi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Dopamine plays a number of important physiological roles. However, activation of dopamine receptor type-5 (DR5) and its effect in renal epithelial cells have not been studied. Here, we show for the first time that DR5 is localized to primary cilia of LLCPK kidney cells. Renal epithelial cilia are mechanosensory organelles that sense and respond to tubular fluid-flow in the kidney. To determine the roles of DR5 and sensory cilia, we used dopamine to non-selectively and fenoldopam to selectively activate ciliary DR5. Compared to mock treatment, dopamine treated cells significantly increases the length of cilia. Fenoldopam further increases the length of …

Β-Lactam Estrogen Receptor Antagonists And A Dual-Targeting Estrogen Receptor/Tubulin Ligand, Niamh O'Boyle, Jade K. Pollock, Miriam Carr, Andrew Js Knox, Seema M. Nathwani, Shu Wang, Laura Caboni, Daniela M. Zisterer, Mary Meegan

Articles

Twelve novel β-lactams were synthesised and their antiproliferative effects and binding affinity for the predominant isoforms of the estrogen receptor (ER), ERα and ERβ, were determined. β-Lactams 23 and 26 had the strongest binding affinities for ERα (IC₅₀ values: 40 and 8 nM respectively) and ERβ (IC₅₀ values: 19 and 15 nM). β-Lactam 26 was the most potent in antiproliferative assays using MCF-7 breast cancer cells, and further biochemical analysis showed that it caused accumulation of cells in G₂/M phase (mitotic blockade) and depolymerisation of tubulin in MCF-7 cells. Compound 26 also induced apoptosis and downregulation …