Chemicals and Drugs Commons^™

Design And Synthesis Of Novel Sultams As Non-Nucleoside Inhibitors Of Hiv Reverse Transcriptase, Brian Chadwick Lecroix

Doctoral Dissertations

The compound 2-methyl-3-phenyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxide (NSC 108406) was identified as an HIV-1 reverse transcriptase inhibitor by the National Cancer Institute. Using this lead, the Baker group has developed a series of analogues with various groups at the 3-position that show a spectrum of biological activities. In the end, the substituents used could not compare to the biological activity of the inhibitor efavirenz (Sustiva^® [trademark]), and so it was decided to synthesize sultams with alkylethynyl substituents at the 3-position of the sultams in an attempt to mimic the activity of efavirenz.

Previous research analyzed the proposed novel sultams in the modeling …

Ionic Conductivity In Non-Ionic Compounds, Usha Kranthi Avala

Masters Theses & Specialist Projects

The main objective of this work is to investigate the ionic conductivity of the drugs under certain conditions and also to compare the ionic conductivities of drugs determined by single surface sensors and parallel plate sensors. The ionic conductivity of various materials at their pre-melt and melt states are studied in order to further study a recently discovered phenomenon. Polar solids like Lidocaine, Ketoconazole, Procainamide and Nifedipine were examined in this study. Experimental studies show an increase in ionic conductivity in both pre-melt (20 -30 °C below melting temperature) and melt transition regions. Results of ionic conductivity of both parallel …

Developing Thyronamine Analog Pharmaceuticals Targeting Taar1 To Treat Methamphetamine Addiction, Troy Andrew Wahl

Dissertations and Theses

As a part of the overall program in the Grandy laboratory at Oregon Health & Science University (OHSU), studying the underlying chemical biology of methamphetamine (Meth) addiction, this dissertation reports on the development of six new thyronamine analogs which were synthesized and assayed against trace amine associated receptor 1 (TAAR1), giving preliminary results consistent with the analogs being inverse agonists. Due to highly variable TAAR1 expression levels in the assays, based on inter-assay response to control Meth stimulation as well as other possible factors, kinetic models were developed to qualitatively explain the assay results. The models set approximate limits on …

Comparison Of Methodologies For Synthesis Of 3-(Cyclopropylethynyl)Benzisothiazole 1,1-Dioxide, Rachel Lee Naramore

Chancellor’s Honors Program Projects

No abstract provided.

Dimethyl Sulfoxide (Dmso) Exacerbates Cisplatin-Induced Sensory Hair Cell Death In Zebrafish (Danio Rerio), Phillip M. Uribe, Melissa A. Mueller, Julia S. Gleichman, Matthew D. Kramer, Qi Wang, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger, Douglas A. Cotanche, Jonathan I. Matsui

Chemistry Faculty Publications and Presentations

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells …

Lyrica, Shannon Hayward

Natural Sciences Student Research Presentations

Illustrates the chemical components of Lyrica, a pain management medication.

Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, Jeanethe Anguizola, K. S. Joseph, Omar S. Barnaby, Ryan Matsuda, Guadalupe Alvarado, William Clarke, Ronald Cerny, David S. Hage

David Hage Publications

This report used high-performance affinity microcolumns to examine the changes in binding by sulfonylurea drugs to in vivo glycated HSA that had been isolated from individual patients with diabetes. An immunoextraction approach was developed to isolate HSA and glycated HSA from clinical samples, using only 20 μL of plasma or serum and 6–12 nmol of protein to prepare each affinity microcolumn. It was found that the affinity microcolumns could be used in either frontal analysis or zonal elution studies, which typically required only 4–8 min per run. The microcolumns had good stability and allowed data to be obtained for multiple …

Structural Basis For Enzyme I Inhibition By Α-Ketoglutarate, Vincenzo Venditti, Rodolfo Ghirlando, G. Marius Clore

Vincenzo Venditti

Creating new bacterial strains in which carbon and nitrogen metabolism are uncoupled is potentially very useful for optimizing yields of microbial produced chemicals from renewable carbon sources. However, the mechanisms that balance carbon and nitrogen consumption in bacteria are poorly understood. Recently, α-ketoglutarate (αKG), the carbon substrate for ammonia assimilation, has been observed to inhibit Escherichia coli enzyme I (EI), the first component of the bacterial phosphotransferase system (PTS), thereby providing a direct biochemical link between central carbon and nitrogen metabolism. Here we investigate the EI-αKG interaction by NMR and enzymatic assays. We show that αKG binds with a KD …

Structure, Dynamics And Biophysics Of The Cytoplasmic Protein–Protein Complexes Of The Bacterial Phosphoenolpyruvate: Sugar Phosphotransferase System, Vincenzo Venditti

Vincenzo Venditti

The bacterial phosphotransferase system (PTS) couples phosphoryl transfer, via a series of bimolecular protein–protein interactions, to sugar transport across the membrane. The multitude of complexes in the PTS provides a paradigm for studying protein interactions, and for understanding how the same binding surface can specifically recognize a diverse array of targets. Fifteen years of work aimed at solving the solution structures of all soluble protein–protein complexes of the PTS has served as a test bed for developing NMR and integrated hybrid approaches to study larger complexes in solution and to probe transient, spectroscopically invisible states, including encounter complexes. We review …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …