Pharmacology Commons^™

Reversible, Light-Controlled Inhibition Of Stim1-Mediated Calcium Signaling Using Photoswitchable Ml-9 Derivatives In Jurkat-Lucia Nfat Reporter T Cells, José L. Matute Gálvez

Honors Scholar Theses

Store-operated calcium entry (SOCE) through calcium release-activated

calcium (CRAC) channels is the dominant pathway for sustained Ca2+ influx in

non-excitable cells and is essential for T cell activation, driving downstream

signaling through the calcineurin-NFAT transcriptional axis. Dysregulation of

SOCE produces multi-systemic disease phenotypes, establishing that precise,

spatiotemporally controlled modulation of this pathway is a fundamental

therapeutic requirement. ML-9 is one of the only characterized small molecules

capable of targeting SOCE upstream at the level of STIM1 localization, but lacks

the selectivity, pharmacokinetic properties, and spatiotemporal control necessary

for therapeutic development.

This work describes the design, synthesis, and biological evaluation of …

In Vitro Pharmacological Evaluation Of Novel Cmpi Derivatives As Selective Positive Allosteric Modulators Of The Alpha4 Beta2 Nicotinic Acetylcholine Receptor, Josue Gaona, Nataly Sanchez, Wilder Felix, Nathalia Menegasso, Brisa Cea, Ganesh Thakur, Ayman K. Hamouda

School of Medicine Student Publications and Presentations

Nicotinic acetylcholine receptors (nAChRs) contribute to the pathogenesis of neurodegenerative diseases such as Parkinson’s disease (PD), where degeneration of dopaminergic and cholinergic neurons disrupts neurotransmission. The (α4)₃(β2)₂ nAChR subtype is expressed on affected neuronal populations and represents a promising therapeutic target. Positive allosteric modulators (PAMs) may enhance receptor function while preserving endogenous signaling. We evaluated chemical derivatives of CMPI [3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrazol-4-yl)isoxazol] as selective PAMs of (α4)₃(β2)₂ nAChRs. Two-electrode voltage-clamp recordings were performed in Xenopus laevis oocytes expressing defined receptor stoichiometries to assess potentiation and generate dose–response curves. Cytotoxicity was assessed in HEK cells using the MTT assay. Substitutions at the pyrazole …

Substituted Piperidines As (Alpha4)3(Beta2)2 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators: In Vitro Pharmacology, Nataly Sanchez, Josue Gaona, Wilder Felix, Nathalia Menegasso, Brisa Cea, Ganesh Thakur, Ayman K. Hamouda

School of Medicine Student Publications and Presentations

Nicotinic acetylcholine receptors (nAChRs) play a crucial role in the pathogenesis of neurodegenerative diseases such as Parkinsonʼs disease (PD). In PD, degeneration of dopaminergic and cholinergic neurons impairs neurotransmitter release, leading to cognitive and motor dysfunction. Current treatments provide only symptomatic relief, highlighting the need for novel therapeutic strategies. The (α4)₃(β2)₂ subtype of nAChRs is expressed on affected neurons, making it a promising druggable target for enhancing neurotransmitter release and providing neuroprotection. To explore the therapeutic potential of positive allosteric modulators (PAMs) of (α4)₃(β2)₂ nAChRs, we evaluated chemical derivatives of CMPI [3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrazol-4-yl)isoxazole]. We used two-electrode voltage-clamp recordings from Xenopus laevis …

Identification Of Fentanyl And Fentanyl Analogs Found In Human Urine Using Gas Chromatography-Mass Spectrometry, Adam M. Fisher

Electronic Theses & Dissertations (2024 - present)

Identification of fentanyl and its analogs in unknown samples is a frequent practice completed in forensic crime labs, as the fentanyl epidemic continues. With the continued increase in illicit drug use, crime labs are not able to keep up with the flooding of new fentanyl analogs being developed, resulting in new analogs slipping past the crime labs’ authority. This research is to start to develop a database of commonly found fentanyl analogs in New York State. Gas Chromatography-Mass Spectrometry (GC-MS) is a widely used method for the detection and identification of illicit drugs in forensic crime labs. A database that …

Nanoparticles As Antioxidant Agents: A Comprehensive Review, Sulyman Olalekan Ibrahim, Halimat Yusuf Lukman, Fatimat Ronke Abdulkadir, Monsurat Yemisi Bello, Yusuf Oloruntoyin Ayipo, Halimah Funmilayo Babamale, Marili Funmilayo Zubair, Olubunmi Atolani

Al-Bahir

This study seeks to provide a comprehensive overview of the latest progress in the antioxidant properties of nanoparticles. Nanoparticles (NPs) have emerged as a promising tool in several domains of science and industry, including their application as antioxidant agents. The main knowledge gaps seem to be in correctly identifying the make-up of the naturally occurring phytochemicals that give these nano-antioxidants their extraordinary pharmacology and drug-like properties. In many instances, that characterization is done using spectroscopy instrumentation such as fourier-transform Infrared (FT-IR), scanning electron microscope (SEM), and X-ray diffraction analysis (XRD). From literature appraisals, it was discovered that a lot of …

Heavy Metals Analysis And Physicochemical Characterization Of Groundwater At A Battery Recycling Site In South-Western Nigeria, Adeniyi T. Adeleke, Rasaki K. Odunaike, Shamsideen K. Alausa, Idris O. Olayiwola, Adetoro T. Talabi, Qasim A. Adeniji, Adejumobi C. Adeniyi

Tanzania Journal of Science

Indiscriminate dumping of battery waste is a huge issue that endangers human health and the environment. This study aimed at analysing the health impacts of exposure to pollution from spent battery recycling in Ogun State, which houses a diverse range of battery recycling industries. At this study site, forty water samples were studied over the Wet and Dry seasons to assess the impact of battery recycling waste on groundwater. Except for the TSS, the physiochemical parameters of the groundwater vary with season and are within the permissible limits. The electrical conductivity (EC), turbidity, Phosphorus, Biochemical oxygen demand (BOD), Dissolve oxygen …

Photoluminescence Switching In Quantum Dots Connected With Fluorinated And Hydrogenated Photochromic Molecules, Ephraiem S. Sarabamoun, Jonathan M. Bietsch, Pramod Aryal, Amelia G. Reid, Maurice Curran, Grayson Johnson, Esther H. R. Tsai, Charles W. Machan, Guijun Wang, Joshua J. Choi

Chemistry & Biochemistry Faculty Publications

We investigate switching of photoluminescence (PL) from PbS quantum dots (QDs) crosslinked with two different types of photochromic diarylethene molecules, 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (1H) and 4,4'-(1-perfluorocyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (2F). Our results show that the QDs crosslinked with the hydrogenated molecule (1H) exhibit a greater amount of switching in photoluminescence intensity compared to QDs crosslinked with the fluorinated molecule (2F). With a combination of differential pulse voltammetry and density functional theory, we attribute the different amount of PL switching to the different energy levels between 1H and 2F molecules which result in different potential barrier …

Design Of Kappa Opioid Receptor Agonists For Potential Treatment Of Multiple Sclerosis, Lindsay Kornberger

Theses and Dissertations--Pharmacy

Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system characterized by demyelination and neuroinflammation. There is currently no cure for MS. There is a critically unmet need for the development of pharmacotherapies that can induce remyelination promoting both repair and recovery. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating pharmacotherapies. KOR activation has been shown to promote functional recovery and remyelination preclinically. However, typical KOR agonists like U50,488 have limitations such as sedation and dysphoria limiting their use. This necessitates further development of new KOR agonists that maintain …

Development Of An Lcms Method To Detect And Quantify Curcumin In A Novel Oral Formulation Of Turmeric, Brandon Renninger

Annual Research Symposium

No abstract provided.

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Wastewater-Informed Public Health Intervention Playbook

Sustain Magazine

As the SARS-CoV-2 pandemic quickly spread from country to country and continent to continent in 2020, governments and scientists needed a way to track COVID-19 through populations in order to position public health interventions in the most impactful locations. Having a decision-based risk framework may help to guide policy creation that could minimize or prevent possible outbreaks and surges of infection within communities. The University of Louisville in partnership with Louisville’s Department of Public Health and Wellness tested this strategy in 2021 and 2022. This Wastewater-Informed Public Health Intervention Playbook describes the decisions and actions of that academic and public …

Exploring Pathways From Data To Knowledge To Insights In The Pharmaceutical Industry: ‘Introducing The Pharmaceutical Knowledge Ecosystem’, Melanie J. Adams, Paige E. Kane, Anne Greene (Editor), Martin Lipa

Level 3

The ecosystem of how the pharmaceutical industry acquires data, transforms these data into tangible knowledge, and derives valuable insights throughout the process, is highly complex. Data, information, knowledge, and the resulting insights, are necessary to support decision- making, manage risk, problem solve, ensure product realisation, enable continual improvement, and enhance operational effectiveness. Building on the fundamental concepts established in the well-known Data Information Knowledge Wisdom (DIKW) hierarchy, this paper reviews the basic concepts involved in the DIKW pathway and begins to relate these concepts to both established capabilities (e.g., PAT), existing requirements (e.g., data integrity), and emerging trends in the …

Improving Risk-Based Decision Making (Rbdm) Effectiveness Through A Framework Which Integrates Knowledge And Risk, Martin Lipa, Valerie Mulholland, Anne Greene (Editor)

Level 3

This paper explores the emergence of the importance of knowledge in Risk-Based Decision Making (RBDM) and Quality Risk Management (QRM) through a detailed review of ICH Q9(R1) (Step 2) and presents a framework(the RKI cycle) to integrate knowledge and risk and associated six principles to operationalise it.

Wastewater-Based Estimation Of Substances Discharged At The Rest Areas Along The State Highways In Kentucky, Katherine E. Gray, Eugene Shin, Tyler Whitt, Andrew Windhorst, Houston Hampton, Chris Delcher, Bikram Subedi

Posters-at-the-Capitol

The availability of licit and illicit stimulants and its adverse consequences on public health has emerged as a major drug threat to communities in the United States. Despite several drug-involved traffic incidents along the interstate highways, this report represents the first comprehensive and quantitative report of drugs discharged at the rest areas along the interstate highways. In this National Institute of Justice-funded study, the amount of several discharged drugs focusing on stimulants but also including opioids and prescription antipsychotics are being measured in raw wastewater collected from five rest areas and a truck servicing facility using a state-of-the-art mass …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Behavioral Screening And Chiral Bioanalysis Of Emerging Stimulant-Type Drugs In Rats, Tyson R. Baird

Theses and Dissertations

The epidemic of drug use in the United States and elsewhere in the world has resulted in tragic loss of life and substantial economic costs. Novel psychoactive substances (NPS) are one of the contributors to this problem, and the lack of information about many of these drugs compounds their risk. This dissertation proposes a strategy to use intracranial self-stimulation (ICSS) as a behavioral screening tool to assess emerging drugs of abuse for their abuse potential in order to generate a proactive threat assessment. A series of stimulant-type drugs including methcathinone, α-pyrrolidinohexanophenone (α-PHP), cocaine, and the phenyltropane analogs of cocaine WIN35428 …

Synthesis Of New Anilinoquinazoline Derivatives As Potential Anticancer Agents: Antiproliferative Activity, Molecular Docking And Molecular Dynamics Studies, Muhammad Kumayl Abdul Wahab

Student Works (2020-2029)

Current reversible epidermal growth factor (EGFR) tyrosine kinase inhibitors of the non-small cell lung cancer (NSCLC) have been resisted by T790M mutation, while irreversible inhibitors introduced to overcome the mutation have faced resistance from C797S mutation. In the effort to discover potential reversible EGFR inhibitors, two series of anilinoquinazoline derivatives were synthesized and characterized, studied for their in vitro antiproliferative activity against NSCLC cell lines, namely A549, H1650 and H1975, and studied for the plausible binding mode in epidermal growth factor receptor kinases with different mutations through molecular docking. In the first series, the anilinoquinazoline scaffold was derivatized through the …

Melanogenesis, Its Regulatory Process, And Insights On Biomedical, Biotechnological, And Pharmacological Potentials Of Melanin As Antiviral Biochemical, Toluwase Hezekiah Fatoki, Omodele Ibraheem, Catherine Joke Adeseko, Boluwatife Lawrence Afolabi, Daniel Uwaremhevho Momodu, David Morakinyo Sanni, Jesupemi Mercy Enibukun, Ibukun Oladejo Ogunyemi, Akinwunmi Oluwaseun Adeoye, Harriet U. Ugboko, Amoge Chidinma Ogu, Abiodun Samuel Oyedele, Adejoju Omodolapo Adedara, Abiodun Joseph Jimoh, Oluwakemi Ruth Ogundana, Oritsetimeyin Eworitse Ebosa

Chemistry Student Research

Melanin is s most widely distributed pigment and is found in bacteria, fungi, plants, and animals. Melanogenesis is under complex regulatory control by multiple agents interacting through pathways activated by hormonal and receptor-dependent and -independent mechanisms. There are about 20 genes that are involved in the biochemical pathway of melanogenesis and its regulation, which include: tyrosinase, microphthalmia-associated transcription factor, melanocortin1 receptor, adenylate cyclase, protein kinase A. Human melanogenesis regulatory proteins such as MAPK1, CREB3, and CREBP, have binary interaction with the protein of herpesvirus, hepatitis C virus, Human immunodeficiency virus type 1, Simian virus 40, and Human adenovirus A and …

The Analytical And Biomedical Applications Of Carbon Dots And Their Future Theranostic Potential: A Review, Sukunya Ross, Ren-Siang Wu, Shih-Chun Wei, Gareth M. Ross, Huan-Tsung Chang

Journal of Food and Drug Analysis

In recent years, carbon dots (C-dots) have gained appreciable interest owing to their unique optical properties, including tunable fluorescence, stability against photobleaching and photoblinking, and strong fluorescence. Simple and low-cost hydrothermal and electrochemical approaches have been widely used in the preparation of biocompatible and high-quality C-dots. Various C-dots have been used for the quantitation of small analytes, mostly based on analyte induced fluorescence quenching. Depending on the nature of precursors, synthetic conditions (such as reaction temperature and time), and surface conjugation, multi-function C-dots can be prepared and used in diagnostics and therapeutics. Their strong fluorescence and photostability, enables use in …

Comparison Of Centrifugation And Solid Phase Extraction (Spe) Methods Of Sample Preparations In Determination Of Residues Of Drugs Of Abuse In Urine, John Mahugija, Anastazia Wandwi, Kessy Kilulya

Tanzania Journal of Science

Detection of drugs of abuse in urine samples depends on their composition, absorption, distribution, physical and chemical properties, concentrations, elimination properties, and the techniques employed. This study compared the performance of centrifugation and solid phase extraction (SPE) methods in the determination of levels of drugs of abuse and their metabolites in urine samples collected from drug abusers. Analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Calibration was done using both internal and external standards. The recovery values were generally greater in centrifugation method than in SPE method, but the recoveries in both methods were within an acceptable range. Linearity …

Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon

Electronic Theses and Dissertations

This thesis describes the isolation, structure elucidation, and synthesis of natural products from marine cyanobacteria. A crude extract from a cyanobacterium collected in Curacao showed selective affinity for the dopamine D₅ receptor in a screen against a panel of CNS receptors. Due to the high similarity of the D₅ and D₁ receptor, to date there are no known ligands that differentiate them. Attempts to purify the compound responsible for this affinity led to the isolation of the known compound caylobolide A. A second extract from a cyanobacterium collected in Panama underwent bioassay-guided fractionation and yielded the novel …

Innovative Approaches In The Discovery Of Aquatic Mycobacteriophages, Janis H. Doss

Biomedical Sciences Theses & Dissertations

Bacteriophages (phages), viruses that infect bacteria, have many applications in medicine, agriculture, molecular biology, and other fields. As antibiotic resistance becomes an increasing problem, interest in phages has grown. The traditional techniques of phage discovery are successful for some phages, but others require modified procedures to achieve detectable host infection.

Mycobacterium is a diverse bacterial genus characterized by a unique cell wall containing mycolic acids, which aids in survival and pathogenesis. The aims of the present research were to isolate mycobacteriophages, use bioinformatics techniques to analyze mycobacterial prophages, and combine genetic analysis with multi-well plate host range studies to identify …

Sustainable Solutions, Fall/Winter 2020, Issue 41

Sustain Magazine

No abstract provided.

Environmentally Responsible Land Use, Spring/Summer 2010, Issue 22

Sustain Magazine

No abstract provided.

Sustainable Communities, Fall/Winter 2010, Issue 21

Sustain Magazine

No abstract provided.

Sustainable Building, Spring/Summer 2009, Issue 20

Sustain Magazine

No abstract provided.

Environmental History, Fall/Winter 2009, Issue 19

Sustain Magazine

No abstract provided.

Student Research, Spring/Summer 2008, Issue 18

Sustain Magazine

No abstract provided.

Evolving Pollution Prevention, Fall/Winter 2008, Issue 17

Sustain Magazine

No abstract provided.

Climate Change, Spring/Summer 2007, Issue 16

Sustain Magazine

No abstract provided.