Chemicals and Drugs Commons^™

Characterization Of The Microbial Phosphonate-Activating Pntc Enzymes, Kyle Rice

Theses and Dissertations (Comprehensive)

New strategies are urgently needed to combat infectious diseases in an era of rising antibiotic resistance. Furthermore, an emerging appreciation for the human microbiome’s role in maintaining health motivates discovery of species-specific antibiotics that minimally disrupt our native bacterial communities. Small molecule modifications to bacterial cell surfaces represent a potentially rich source of new targets for next generation antibiotics, as these molecules mediate virulence and evasion of the host immune response. Phosphocholine (PCho) is a rare cell surface modification that contributes to virulence, and modifications with phosphonates like 2-aminoethylphosphonate (AEP) are even more unusual and therefore provide opportunities for species- …

Crystal Structure Of Vapbc-1 From Nontypeable Haemophilus Influenzae And The Effect Of Pin Domain Mutations On Survival During Infection, Ashley L. Molinaro, Maithri M. Kashipathy, Scott Lovell, Kevin P. Battaile, Nathan P. Coussens, Min Shen, Dayle A. Daines

Biological Sciences Faculty Publications

Toxin-antitoxin (TA) gene pairs have been identified in nearly all bacterial genomes sequenced to date and are thought to facilitate persistence and antibiotic tolerance. TA loci are classified into various types based upon the characteristics of their antitoxins, with those in type II expressing proteic antitoxins. Many toxins from type II modules are ribonucleases that maintain a PilT N-terminal (PIN) domain containing conserved amino acids considered essential for activity. The vapBC (virulence-associated protein) TA system is the largest subfamily in this class and has been linked to pathogenesis of nontypeable Haemophilus influenzae (NTHi). In this …

In Vitro Metabolism Of The Synthetic Cannabinoids Px-1, Px-2, Px-3 And A Comparison Of Their Clearance Rates In Human Liver Microsomes, Travon Cooman

Graduate Theses, Dissertations, and Problem Reports

Detection of SCs in body fluids continue to be a challenge because of limited metabolism data, lack of standards and reference mass spectrometry data. In vivo and in vitro experiments help elucidate metabolite markers for novel psychoactive substances and can prompt synthesis of standards to verify proposed metabolites. In this study, metabolism of three SCs N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamine (PX-1), N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluropentyl)-1H-indazole-3-carboxamide (PX-2), and N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (PX-3) were investigated using human liver microsomes. Previous studies showed PX-3 as the most potent CB1 and CB2 receptor agonist.

Half-life and clearance data were acquired using liquid chromatography- tandem mass spectrometry. Metabolite elucidation was performed using liquid chromatography …

Development Of A Chemical Genetic Screen To Identify Compounds That Enhance Laromustine Cytotoxicity, Xiaoou Wang

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials against acute myeloid leukemia. Though laromustine showed some success in clinical trials, more experiments are needed to understand the hematological toxicity and the molecular mechanisms of patients’ resistance. This project aims to develop a strategy to identify compounds synergistic with laromustine in cultured leukemia cells from a library of 450 FDA-approved compounds through a forward chemical genetic screen. To optimize the screen, the cell seeding density, doubling time, and dose response curves were determined. The optimized concentration of HL60 cells in these experiments was determined to be between 25,000 and …

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …

The Effects Of Medical Cannabis Use Among Adults With Chronic Pain: An Integrative Review Of The Literature, Bridget A. Asevedo

Honors Undergraduate Theses

The purpose of this integrative literature review was to understand the effects of medical cannabis for chronic pain management in adults. Anecdotal reports suggest the use of medical marijuana as a pain management therapy could be an alternative to opioids and other medications which have long term consequences. Potential uses span the health care continuum, from prescribed outpatient symptom management, to acute care, extended care, home care, and hospice treatment settings. The methodology included a review and synthesis of relevant research articles from 2012 to 2018, written in the English language. The findings suggest medical cannabis has the potential of …