Chemicals and Drugs Commons^™

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the nanoparticles formed ...

Discovery Of Sigma-2 Ligands And Prioritization Of Marine Cyanobacteria Extracts For Tnbc Drug Discovery, Katelyn Grenell, Andrea L. Rague, Sahar Mofidi, Jane E. Cavanaugh, Kevin J. Tidgewell

Undergraduate Research and Scholarship Symposium

The role of natural products in drug development is well established. In recent years, marine cyanobacteria have been regarded as a major source of biologically active metabolites with chemical and Figure 5 pharmacological diversity. These cyanobacterial natural products serve as a promising source of drug A. leads for the discovery of therapeutic agents used in the treatment of many diseases of interest, such as CNS disorders, pain, and cancer. We have generated a library of 409 fractions from 37 field collected cyanobacterial samples and screened these fractions against a panel of CNS receptors using radiolabeled ligand competitive-binding assays. Upon analysis ...

Synthesis, Characterization, And Bioactivity Of 3-Substituted Coumarins As An Undergraduate Project, Karsen King, Nicholas Campbell, Ronald Okoth, Wathsala Medawala

Georgia Journal of Science

Coumarins are an important class of phytochemicals, a chemical defense presumed to be secreted by plants. More recently, Coumarins have gathered popularity for their basis in anti-cancer agents. This paper dives into the organic synthesis of two 3-substituted coumarins from o-vanillin using the Knoevenagel condensation reaction. The 3-substituted coumarin were characterized using melting point analysis, ¹H-NMR, and UV-Vis spectroscopy. In addition, the anticancer activity of synthesized 3-substituted coumarin compounds were assayed against topoisomeraseIIα, which is the target enzyme of FDA approved anti-cancer drug etoposide since it is an active enzyme in cancer cell replication. The demonstrated procedures can be ...

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa ...

The Synthesis And Characterization Of Ionic Liquids Using Nitrogen-Based Cations For Transdermal Delivery, Jo Galloway

Honors Theses

The purpose of this research was to explore the synthesis mechanisms of water-soluble ionic liquids with nitrogen-containing cationic bases for future use in transdermal drug delivery and forensic science applications. Ionic liquids are salts with an organic cation and either an organic or inorganic anion. They have asymmetric structures, which means that the molecules don’t pack together as neatly as other salts do, therefore, they don’t crystallize as easily, and their melting points are lower. Ionic liquids have melting points below 100°C, and many are liquid at room temperature. Mechanistic studies reveal that the potency of ILs ...

The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman

Honors College Theses

For the past few years, the COVID-19 pandemic has been the focal point in healthcare and research. This disease has permanently changed daily life and left a historic impact on the world. Most people have felt the effects of this pandemic either directly, via infection, or indirectly, via change in workflow, financial impact, etc. The main question for this virus still remains today; how do we treat this illness effectively? While many ideas are being tested and suggested, a definite answer has yet to be procured. Vaccine rates are climbing on a daily basis, serving as the first and most ...

2-Deoxy-D-Glucose As India’S Response To Covid-19: A Commitment Or Conceit?, Ritwik Ghosh, Dipayan Roy, Subhankar Chatterjee, Julián Benito-León

Journal of Community Hospital Internal Medicine Perspectives

2-deoxy-D-glucose (2-DG) has recently been approved to treat moderate to severe COVID-19 patients in India. Here we discuss whether this is a well-thought-out step towards the long-term management of COVID-19 or a decision taken at the spur of the moment. 2-DG, an anticancer drug, also has immunomodulatory functions. Several studies have shown 2-DG to inhibit viral replication and cytokine storm. However, these findings are mostly on cells and animal models. The clinical trial that has become the basis of the approval of this drug in India is yet to be peer-reviewed and has not explicitly addressed several concerns, nor has ...

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test ...

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as ...

Drug-Facilitated Sexual Assault At The University Of Arkansas, Barrett Weidman

Chemical Engineering Undergraduate Honors Theses

This work was written to fulfill two main purposes. First, to help survivors of Drug-Facilitated Sexual Assault (DFSA) process their experience by compiling the toxicological, pharmacological, and distribution of the three most used date-rape drugs. Second, to gauge the knowledge and interest of University of Arkansas students regarding drug impairments, sexual assault education, and bystander intervention training. A survey was conducted for the latter and revealed that 91.6% of students believe the University’s existing sexual assault prevention education and bystander intervention training have room for improvement. Also, 37.1% of students who have received this education report that ...

“Translation Of Hdac6 Pet Imaging Using [18f]Ekz-001 – Cgmp Production And Measurement Of Hdac6 Target Occupancy In Nhps” – A Review, Dania Rahal

Chemistry & Biochemistry Undergraduate Honors Theses

The inhibition of histone deacetylase 6 (HDAC6) has been reported to alleviate the effects of neurodegenerative diseases such as Alzheimer’s disease. The brain-penetrant PET radioligand [¹⁸F]EKZ-001 has high affinity and selectivity towards HDAC6 and therefore suggests great promise in therapeutic treatment studies and development for neurodegenerative diseases. “Translation of HDAC6 PET imaging using [¹⁸F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs” has achieved an effective, fully automated method of producing [¹⁸F]EKZ-001 in compliance with current good manufacturing practices (cGMP) to support the translation of [¹⁸F]EKZ-001 PET for first-in-human ...

The Use Of Hallucinogens In The Treatment Of Mental Health Disorders, Brianna Gagen

Honors College Theses

The percent of people with mental health disorders in the United States have skyrocketed over the past decade. With stigma surrounding the discussion of mental health and the symptoms associated with it, often those that are suffering do not receive sufficient treatment, as they might with a physical illness. The current, common treatment options for common psychological disorders, like depression, anxiety, and post-traumatic stress disorder, are sometimes not effective in patients, due to resistance or poor response outcomes. Consequently, in order to research alternative therapeutic approaches for mental health disorders, scientists are researching the effects of several hallucinogenic drugs in ...

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

The opioid epidemic impacted over 12 million Americans in 2019. Although they are effective pain-relieving medications, they carry addictive and dangerous side effects. Opioids, like morphine, bind non-selectively in both central and peripheral tissues; however, dangerous side effects result from central activation. Inflamed conditions of injured tissues have a lower pH (pH=6-6.5) environment than healthy central tissue (pH=7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using computationally-based molecular extension and dissection techniques. Binding to the mu-opioid receptor (MOR) is dependent on protonation of the biochemically active amine group of morphine ...

Integration Of Medicinal Fungi Into The Heber W. Youngken Jr. Medicinal Garden, Anthony Makashov

Senior Honors Projects

The Heber W. Youngken Jr. Medicinal Garden is a one-of-a-kind resource that houses close to 300 medicinal plants and is filled to the brim with educational opportunities. For the College of Pharmacy, this garden has been the centerpiece of many classes taught here at the University of Rhode Island and has roots as a physical teaching space. While the garden contains a plethora of plant species, medicinal fungi have yet to have been included in the garden, despite their relevance as both sources of pharmaceutical drug discovery and as natural products with inherent physiological benefits themselves. The purpose of my ...

Unveiling The Opioid Crisis: The Impact Of Opioids On Body Systems And Alternative Treatment Options To Reduce The Nationwide Opioid Epidemic, Krishna S. Patel, Elizabeth A. Manheim Ph.D.

Kean Quest

No abstract provided.

Frequency Of Marijuana Use By California University Students Based On Gender And Ethnicity: A Quantitative Analysis, Evelyn Lorraine Anderson

Doctoral Dissertations and Projects

The purpose of this quantitative causal-comparative study was to determine the frequency of marijuana use by California university students based on gender and ethnicity. This study was important because marijuana is the most used illicit substance in the United States, and there is limited research regarding the demographic characteristics of California university students who use marijuana. The quantitative research design was used to describe the patterns of marijuana use by California university students. The setting was online. The participants included a random sample of 167 college students from five California state universities. The Daily Sessions, Frequency, Age of Onset, and ...

Estimating The Analytical Performance Of Raman Spectroscopy For Quantification Of Active Ingredients In Human Stratum Corneum, Hichem Kichou, Emilie Munnier, Yuri Dancik, Kamilia Kemel, Hugh Byrne, Ali Tfayli, Dominique Bertrand, Martin Soucé, Igor Chourpa, Franck Bonnier

Articles

Confocal Raman microscopy (CRM) has become a versatile technique that can be applied routinely to monitor skin penetration of active molecules. In the present study, CRM coupled to multivariate analysis (namely PLSR—partial least squares regression) is used for the quantitative measurement of an active ingredient (AI) applied to isolated (ex vivo) human stratum corneum (SC), using systematically varied doses of resorcinol, as model compound, and the performance is quantified according to key figures of merit defined by regulatory bodies (ICH, FDA, and EMA). A methodology is thus demonstrated to establish the limit of detection (LOD), precision, accuracy, sensitivity (SEN ...

Interactions Among Endothelial Nitric Oxide Synthase, Cardiovascular System, And Nociception During Physiological And Pathophysiological States, Niribili Sarmah, Andromeda M. Nauli, Ahmmed Ally, Surya M. Nauli

Pharmacy Faculty Articles and Research

Nitric oxide synthase (NOS) plays important roles within the cardiovascular system in physiological states as well as in pathophysiologic and specific cardiovascular (CV) disease states, such as hypertension (HTN), arteriosclerosis, and cerebrovascular accidents. This review discusses the roles of the endothelial NOS (eNOS) and its effect on cardiovascular responses that are induced by nociceptive stimuli. The roles of eNOS enzyme in modulating CV functions while experiencing pain will be discussed. Nociception, otherwise known as the subjective experience of pain through sensory receptors, termed “nociceptors”, can be stimulated by various external or internal stimuli. In turn, events of various cascade pathways ...

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.

Zntppea As A Potential Photosensitizer In Photodynamic Therapy, Marly Welborn, Joseph E. Bradshaw

Scholars Day Conference

Photodynamic therapy (PDT) is an emerging treatment that is used against certain types of cancer and other diseases. It functions using a photosensitizer in the presence of light that contributes to cell death in the desired tissues. This research centered on the development of a novel water-soluble porphyrin that could be utilized as a photosensitizer. Using ethanolamine the resulting compound, ZnTPP-EA, was created. Purification and characterization was carried out. The ZnTPP-EA was tested on the A549 lung cancer cell line using an MTT assay under light and dark conditions to assess the compound's effectiveness as a photosensitizer for PDT.