Chemicals and Drugs Commons^™

Synthesis And Characterization Of Polymeric Nanoparticles To Enhance Celleullar Drug Delivery, Rahma Aly

Chemistry Theses

Medicines in the form of nanoparticles called nanomedicines, stand at the forefront of revolutionary advancements in healthcare, offering precise drug delivery and diagnostic capabilities. A recent example of nanomedicine in the clinic is the COVID-19 vaccine, which helped prevent death during the pandemic. While the potential benefits are immense, a myriad of challenges complicate their seamless integration into clinical practice. The design and fabrication of nanoparticles demand meticulous attention to biocompatibility and toxicity. Interactions with biological systems are complex, requiring a delicate balance between therapeutic efficacy and safety. The reticuloendothelial system's rapid clearance of nanoparticles, their instability in physiological environments, …

An Exploration Of The Effectiveness Of Xanthorrhiza Simplicissima And Its Secondary Alkaloids As Antibiotics Against Staphylococcus Aureus With The Use Of Reserpine, Donald Bothe, Savita Chaurasia

Undergraduate Theses

Xanthorhiza simplicissima is a plant that is steeped in medical history. It has been used for hundreds of years by the Native Americans, and later by the Europeans, of Appalachia for its medicinal properties. One of the most useful medical applications of this plant are its antibiotic properties, as typified by its use as a tea that was consumed to treat mouth sores. These antibiotic properties can be attributed to some of its secondary alkaloids such as berberine, liriodenine, oxyacanthine, and magnoflorine. These compounds have been studied in other systems; however, oxyacanthine and magnoflorine have not been researched in tandem …

Chitosan-Based Hydrogels In Drug Delivery, Salma A. Fereig, Mona Mohamed Ahmed Abdelmottaleb

Pharmacy

Hydrogels are three-dimensional cross-linked hydrophilic polymers that are able to absorb large quantities of water and swell. They have various properties like biocompatibility, low toxicity, and mostly biodegradability, which make them attractive for drug delivery applications. Chitosan hydrogels are especially attractive due to the inherent activities of the chitosan itself like the antibacterial, anti-inflammatory, and tissue regeneration enhancement capacity. Therefore, chitosan hydrogels have been proposed for the delivery of various drugs, genes, cytokines, and stem cells via various routes of administration for the treatment of various diseases as well as different forms of degeneration.

Role Of Protein Kinase A And A Kinase Anchoring Proteins In Buffering And Compartmentation Of Camp Signalling In Human Airway Smooth Muscle Cells, Rinzhin T. Sherpa, Karni S. Moshal, Shailesh R. Agarwal, Rennolds S. Ostrom, Robert D. Harvey

Pharmacy Faculty Articles and Research

Background and Purpose

In human airway smooth muscle (hASM) cells, not all receptors stimulating cAMP production elicit the same effects. This can only be explained if cAMP movement throughout the cell is restricted, yet the mechanisms involved are not fully understood. Phosphodiesterases (PDEs) contribute to compartmentation of many cAMP responses, but PDE activity alone is predicted to be insufficient if cAMP is otherwise freely diffusible. We tested the hypothesis that buffering of cAMP by protein kinase A (PKA) associated with A kinase anchoring proteins (AKAPs) slows cAMP diffusion and that this contributes to receptor-mediated, compartmentalized responses.

Experimental Approach

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Ensemble-Based Mutational Profiling And Network Analysis Of The Sars-Cov-2 Spike Omicron Xbb Lineages For Interactions With The Ace2 Receptor And Antibodies: Cooperation Of Binding Hotspots In Mediating Epistatic Couplings Underlies Binding Mechanism And Immune Escape, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with the host cell receptor ACE2 and a panel of diverse class one antibodies. The central objective of this investigation was to examine the molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing of ACE2 binding and antibody evasion for Omicron variants BA.1, BA2, BA.3, BA.4/BA.5, BQ.1.1, XBB.1, XBB.1.5, and XBB.1.5 + L455F/F456L. By combining evolutionary analysis, molecular dynamics simulations, and ensemble-based mutational scanning of spike protein residues in complexes with ACE2, we identified structural stability and binding …

The Fight For Fluoridation In Stl, Noor Yousaf

Undergraduate Research Symposium

Fluoridation is the addition of fluoride to a source of drinking water. In St. Louis’s public water supply, the amount of fluoride remains the same since 1953 at 5ppm. Dr. Ralph Rosen and his team of dentists and researchers advocated for the fluoridation of the water because it reduced the frequency of dental caries occurring in children and adults alike, but the public had opinions on the sudden addition of chemicals to their water. This includes how the public’s health will be affected, how consumer products would change, and also how effective this addition of fluoride would be. This debate …

Killing Cancer: Manipulating Hydrophobic Vanadium Complexes To Improve Anti-Cancer Activity, Levi Ausherman, Debbie C. Crans, Peter A. Lay, Maggi Braasch-Turi

SACAD: Scholarly Activities

Hydrophobic vanadium complexes have recently shown improved anti-cancer activities compared to cisplatin. The hydrophobicity and anti-proliferative activity of [VO(Hshed)(dtb)] ([Hshed= N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethanediamine and dtb= 3,5-di(tert-butyl)catechol)]) have inspired the development of a library of hydrophobic vanadium complexes. Increasing the steric bulk of the catechol ligand has been shown to have a direct impact on hydrophobicity and anti-proliferative activities. Currently at Fort Hays State University, the Braasch-Turi group is synthesizing VO(HSHED)(dtb) to build up material to support the chemical analysis and biological assay performed by our collaborators at Colorado State University and the University of Sydney, Australia, respectively. In the future, we plan …

The Feigned Annoyance And Frustration Test To Activate The Sympathoadrenal Medullary System, Ted W. Gehrig Iii, Lee S. Berk, Robert I. Dudley, Jo A. Smith, Lida Gharibvand, Everett B. Lohman Iii

Physical Therapy Faculty Articles and Research

When perceived as threatening, social interactions have been shown to trigger the sympathoadrenal medullary system as well as the hypothalamic-pituitary-adrenal axis resulting in a physiologic stress response. The allostatic load placed on human health and physiology in the context of acute and chronic stress can have profound health consequences. The purpose of this study was to develop a protocol for a lab-based stress stimulus using social-evaluative threat. While several valid, stress-stimulating protocols exist, we sought to develop one that triggered a physiologic response, did not require significant lab resources, and could be completed in around 10 min. We included 53 …

U.S. Government Agency Podcasts, Bert Chapman

Libraries Faculty and Staff Presentations

Presents podcasts from U.S. Government agencies which can be discovered through the U.S. Government Publishing Office's Catalog of Government Publications. Agencies whose podcasts are presented include the National Institutes of Health, U.S. Peace Corps, U.S. Department of Agriculture, Government Accountability Office (GAO), National Park Service, Department of Justice, Federal Reserve System, and U.S. Naval War College.

Impact Of Fads Genotype On Polyunsaturated Fatty Acid Content In Human Milk Extracellular Vesicles: A Genetic Association Study, John J. Miklavcic, Natalie Paterson, Jennifer Hahn-Holbrook, Laura M. Glynn

Food Science Faculty Articles and Research

Background

Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long-chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk.

Methods

Milk was obtained from a cohort of mothers (N = 70) at 2–4 weeks of lactation. SNPs in the FADS gene locus were determined using …

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Synthesis And Characterization Of Ugi Adducts Of Isatin, Cynthia Domergue, Kimberly Hernandez

Posters - 2024

B-lactam fragments have gathered attention in the chemistry field in being a pharmacophore for medicinal chemistry

- The Ugi reaction involves the reaction of an aldehyde, a primary amine, a carboxylic acid, and an isocyanide to generate α-acetoamido carboxamide derivates (Ugi adducts) -

We focused on the synthesis of the β-lactam derivatives: 1-Benzyl-N-(tert-butyl)-2-oxo-3(2-oxoazetidin-1- yl)indoline-3-carboxamide (4a), N-(tert-Butyl)-2-oxo-3-(2- oxoazetidine-1-yl) indoline-3-carbpxamide (4d) , and N- (tert-Butyl)-1-methyl-2-oxo-3-(2-oxoazetidine-1- yl)indoline-3-carboxamide (4e)

- The Ugi adducts of isatin were synthesized in TFE solvent by stirring the reactant mixture at room temperature and the conversion was monitored by TLC. The solvent was evaporated, and the crude product purified …

Cold Medicine Abuse And Increased Odds Of Recreational Drug Use, Luis Barco

Posters - 2024

Over the counter (OTC) medications are frequently used to address the symptoms associated with common illnesses that affect the public. (SOURCE) Of these OTC medications, cold and cough medications are some of the most widely used. However, cold medications pose a risk in exhibiting different effects depending on which active ingredient is the most prevalent. Dextromethorphan (DXM), one of the most common ingredients in cough medicine, can lead to the development of symptoms that mirror psychosis associated with phencyclidine abuse (1). Though less common, abuse of codeine can also result in the formation of gastric ulcers, internal bleeding, and inflammation …

From Cough To Crip: The Development Of Codeine From A Purely Medical Substance Into A Popular Recreational Drug, Rhett C. Vaughn

Senior Theses

The research that was conducted aimed to elicit the influence that pop culture has on recreational drug consumption. Specifically, the usage of the drug codeine has become very popular in social media among many influencers. The research focuses on the prevalence of this drug across several media platforms, alongside the growing rate of consumption globally. Research was conducted primarily through combining various databases at various organizations and this study aims to compile the data into one coherent paper regarding codeine in pop culture. While, it cannot be solely attributed to one specific outlet or influence, this study found that alongside …

Detailing The Effects Of Cannabidiol On Exosome Release In Ewing’S Sarcoma, Bennett Hasley

Theses

Ewing’s sarcoma (ES) is a highly aggressive pediatric cancer found within bone that carries a low five-year survival rate within its patients. This is due, in part, to the cancer’s high malignancy properties as well as the development of resistance to the chemotherapies used to combat this cancer. This project aims to determine if cannabidiol (CBD) has an effect on either exosome release or the protein, signal transducer and activator of transcription 3 (STAT3) within ES cells. Exosomes are vesicles that can carry proteins and other signaling molecules which are released by the cell and allow for cell-to-cell communication. Within …

Accurate Characterization Of Binding Kinetics And Allosteric Mechanisms For The Hsp90 Chaperone Inhibitors Using Ai-Augmented Integrative Biophysical Studies, Chao Xu, Xianglei Zhang, Lianghao Zhao, Gennady M. Verkhivker, Fang Bai

Mathematics, Physics, and Computer Science Faculty Articles and Research

The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs in vivo, leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking. In this study, quantitative structure–kinetics relationship (QSKR) models were developed using 132 inhibitors targeting the ATP binding domain of heat shock protein 90α (HSP90α) to predict the dissociation rate …

An Injectable In Situ Forming Collagen/Alginate/Caso4 Composite Hydrogel For Tissue Engineering Applications: Optimization, Characterization And In Vitro Assessments, Samar A. Salim, Samar A. Salim

Nanotechnology Research Centre

In situ injectable hydrogels are effectively employed to fill irregular cavitary bone defects with initiating bone growth in targeted areas. Herein, an injectable composited hydrogel composed of collagen and alginate cross-linked in situ using different concentrations of calcium sulfate (0.15, 0.3 and 0.6%, wt./v) was synthesized. Recently, CaSO4 is frequently supported as a bone graft material for bone regeneration, owing to its biocompatibility and osteoconductive properties. Moreover, hydroxyapatite (Hap) after salinization-step by (3-Aminopropyl) triethoxysilane (APTES) was incorporated for further enhancing the osteoconductive property of injected hydrogels. All fabricated hydrogels were characterized by SEM, FTIR and XRD analyses. While physiochemical characteristics …

Eco-Friendly Hptlc Determination Of Paracetamol, Caffeine, Drotaverine Hcl And Two Of Their Official Impurities; Application To Assay And Content Uniformity Testing Of Tablet Dosage Form, Samia A. Tawfik, Nariman A. El-Ragehy, Maha A. Hegazy, Ghada A. Sedik

Bulletin of Faculty of Pharmacy Cairo University

The present work is focused on developing and validating an eco-friendly, sustainable and sensitive HPTLC method for the purpose of simultaneous determination of a five component mixture. This mixture includes paracetamol, caffeine, drotaverine HCl and the official impurities of the first two aforementioned drugs, namely; p-aminophenol and theophylline, in order. The developed method is based on application of planar chromatography using a developing system of ethyl acetate: methanol: acetic acid (8:1:2, by volume). Quantitative determination of the mentioned components was performed using UV detection. The parameters impacting chromatographic separation have been optimized. The cited compounds were effectively separated with retardation …

“The Role Of Artificial Intelligence In The Pharmaceutical Field: Enhancing Therapeutic Outcomes And Repurposing Through The Acceleration Of Drug Discovery”, Tonivie Valeriano

[Archive] Belmont University Research Symposium (BURS)

The development of new drugs and their repurposing have considerably benefited the field of pharmacy. It will not only affect the pharmaceutical sector but also its diverse facets of health will be significantly influenced. Yet, the development of innovative medical treatments necessitated a lengthy period of expectancy for human survival. Individual survival rates were decreasing over time before the development of the treatment. Humanity has a limited lifespan. Moreover, investments in new drugs often go unnoticed because of the prolonged and complex process of drug research and development (R&D). In the future of pharmacy, artificial intelligence will continue to have …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …