Pharmacy and Pharmaceutical Sciences Commons^™

Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul

Research Symposium

Background: Hypoxia, a suboptimal level of oxygen, evokes stress response in cells and activated hypoxia signaling has been largely established as a pro-metastasis and pro-angiogenic factor for tumor cells. On the other hand, age-related neurodegenerative disorders are characterized by hypoxic environment, accumulation of molecular garbage and induction of premature senescence. Several recent studies have reported anti-stress impact of the intermittent induction of hypoxia signaling in these cells.

Methods: Screening of a phytochemical library using Hypoxia Responsive Element (HRE) driven luciferase as a reporter was carried out to identify hypoxia-modulating phytochemicals. Activation of HIF-1a (master regulator of hypoxia signaling) was validated …

Oral Dosages Of The Nsaid Aspirin Decreased The Growth Rate Of Species Found In The Human Gut Microbiome Including Akkermansia Muciniphila, Bacteroides Fragilis, Clostridium Sordellii, And Clostridium Difficile, Wyatt H. Greenbaum, Garrett J. Greenbaum, Anna Spiezio

PANDION: The Osprey Journal of Research and Ideas

Over past few decades, new insight has been revealed in the scientific community about the importance of the human gut microbiome relating to general health. It is known that imbalances in the species that reside in the human gut can cause organism-wide problems in humans. When prescribing or injecting oral medications, the thought of the downstream effects on the gut microbiome are not always considered. By exposing known healthy members of the gut; Akkermansia muciniphila, Bacteroides fragilis, Clostridium sordellii, and Clostridium difficile to the Aspirin, this study attempted to provide insight into the effects of the drug on bacterial growth. …

Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal

The Undergraduate Research Journal

Diadema savignyi spine extract in an experimental setup using L929 cell line in vitro. The cell metabolic activity of L929 cells is tested through an MTT assay. The sea urchin spine extract is applied to the cells in two concentrations: 100 μg/ml (136% viability) and 200 μg/ml (95% viability). The bioactive components of the sea urchin spine are identified via GC-MS, and the antioxidant and anti-inflammatory activities are evaluated using catalase assay (CAT), glutathione (GSH), and nitric oxide (NO) tests. Results show that the GC-MS identified bioactive components including the anti-inflammatory and anti-irritant bisabolol oxide and the pro-inflammatory oleic acid. …

Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa

Pharmacy

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and …

Design And Synthesis Of Small Molecule Drugs For Cns Disorders, Kirsten T. Tolentino

Theses & Dissertations

Dopamine (DA) is an important neurotransmitter for the regulation and long-term function of the central nervous system (CNS). DA binds to Dopamine Receptors (DR) to stimulate or inhibit adenyl cyclase production to further elicit a pharmacological response. DRs were cloned, and it was determined that there are two families separated by their function and five total subtypes distinguished by their amino acid structure. The Dopamine 4 receptor (D4R) is the second least studied subtype but has high expression in the frontal cortex, amygdala, hippocampus, hypothalamus, globus pallidus, substantia nigra pars reticula, and thalamus. Dopamine signaling and transmission, especially in the …

July / August 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the July & August 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Α7 Nicotinic Acetylcholine Receptor Interaction With G Proteins In Breast Cancer Cell Proliferation, Motility, And Calcium Signaling, Murat Oz, Justin R. King, Keun-Hang Susan Yang, Sarah Khushaish, Yulia Tchugunova, Maitham A. Khajah, Yunus A. Luqmani, Nadine Kabbani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect …

The Structural Characterization And Bioactivity Assessment Of Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Caraway (Carum Carvi) Seeds, Taibah Aldakhil, Saud O. Alshammari, Bushra Siraj, Bishoy El-Aarag, Shamshad Zarina, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Carum carvi (caraway) of the Apiaceae family has been used in many cultures as a cooking spice and part of the folk medicine. Previous reports primarily focus on the medicinal properties of caraway seed essential oil and the whole seeds extract. However, no effort has been made to study caraway proteins and their potential pharmacological properties, including nonspecific lipid transfer protein (nsLTP), necessitating further research. The current study aimed to characterize nonspecific lipid transfer protein 1 (nsLTP1) from caraway seed, determine its three-dimensional structure, and analyze protein–ligand complex interactions through docking studies. We also evaluated nsLTP1 in vitro cytotoxic …

KCa2 And KCa3.1 Channels In The Airways: A New Therapeutic Target, Razan Orfali, Ali Alfaiz, Mohammad Asikur Rahman, Liz Lau, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

K⁺ channels are involved in many critical functions in lung physiology. Recently, the family of Ca²⁺-activated K⁺ channels (K_Ca) has received more attention, and a massive amount of effort has been devoted to developing selective medications targeting these channels. Within the family of K_Ca channels, three small-conductance Ca²⁺-activated K⁺ (K_Ca2) channel subtypes, together with the intermediate-conductance K_Ca3.1 channel, are voltage-independent K⁺ channels, and they mediate Ca²⁺-induced membrane hyperpolarization. Many K_Ca2 channel members are involved in crucial roles in physiological and pathological …

Cyclic Peptides With Antifungal Properties Derived From Bacteria, Fungi, Plants, And Synthetic Sources, Naiera M. Helmy, Keykavous Parang

Pharmacy Faculty Articles and Research

Fungal infections remain a significant concern for human health. The emergence of microbial resistance, the improper use of antimicrobial drugs, and the need for fewer toxic antifungal treatments in immunocompromised patients have sparked substantial interest in antifungal research. Cyclic peptides, classified as antifungal peptides, have been in development as potential antifungal agents since 1948. In recent years, there has been growing attention from the scientific community to explore cyclic peptides as a promising strategy for combating antifungal infections caused by pathogenic fungi. The identification of antifungal cyclic peptides from various sources has been possible due to the widespread interest in …

May / June 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the May & June 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC₅₀ values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC₅₀ values of 5a–d …

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang

Pharmaceutical Sciences Faculty Publications

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced …

Case Report And Review: Hawthorne Root Toxicity, James Espinosa, Darren Finn, Alan Lucerna

Rowan-Virtua Research Day

Here we present the case of a patient who purchased a hawthorn root product, Raiz de Tejocote, for weight loss purposes. The side effect profile seen, including a positive digoxin level, are consistent with hawthorn root. This case reinforces the importance of asking a patient about all medications, including over the internet medications.

The Effects Of Clonidine On Neonatal Abstinence Syndrome Patient Outcomes, Claire E. Flatt

Chancellor’s Honors Program Projects

No abstract provided.

Death Due To Drug Reaction With Eosinophilia And Systemic Symptoms (Dress) Syndrome: A Case Report, Samantha P. Sternad, Jane Pangburn, Chad Johnston, David Rowe

HCA Healthcare Journal of Medicine

Background

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening, multi-organ adverse drug reaction with an incidence of 1 in 1000 to 1 in 10 000 highrisk drug exposures.

Case Presentation

An elderly female presented to the hospital with progressive weakness and a diffuse erythematous macular rash covering most of her body that started 3 days prior. Over the next 3 days, the patient quickly deteriorated, developing disorientation with acute onset left-sided weakness, leukocytosis, thrombocytopenia, eosinophilia, liver and kidney failure, and hypoxia. Clinical and histological changes supported the diagnosis of DRESS syndrome caused by intravenous (IV) ampicillin …

Reducing Unnecessary Acid Suppression Use In Hospitalized Patients: A Description Of Targeted Strategies Implemented Across A Large Health System, Elizabeth H. Wiggins, L. Hayley Burgess, Joan Kramer

HCA Healthcare Journal of Medicine

Background

Ensuring the appropriate use of proton pump inhibitors (PPIs) and histamine type 2-receptor antagonists (H2RAs) is an important hospital patient safety and quality initiative because therapy may be inappropriately continued during transitions of care. In this article, we aim to describe the impact of targeted quality improvement strategies to reduce unnecessary acid suppression use in hospitalized patients across a large health system.

Methods

Beginning January 1, 2018, focused quality improvement strategies to prevent unnecessary initiation and continuation of proton pump inhibitors (PPIs) and histamine type 2-receptor antagonists (H2RAs) were implemented throughout a large health system. Targeted strategies were initially …

Testing Of Indazole Inhibitors Of Kasa, A Vital Enzyme Of M. Tuberculosis, Karissa Highlander

Student Research Submissions

Tuberculosis is a disease that affects the lungs caused by Mycobacterium tuberculosis (M. tuberculosis). Although drug treatment options exist, increased rates of antibiotic resistant strains have become more prevalent in recent years, driving a need for new treatment approaches. KasA, a β-ketoacyl synthase, has been found to synthesize parts of the cell wall and been identified as an attractive drug target. Previous medicinal chemistry research has been completed to synthesize six effective competitive inhibitors of KasA that would potentially block the enzyme from binding the substrate, preventing elongation of the backbone and creation of the mycolic fatty acids that …

The Application Of Continuous Stationary Phase Gradients To High-Performance Liquid Chromatography And Its Potential To Improve Pharmacological Research, Hannah Klose

Senior Honors Theses

The separation of mixtures into different components is integral to experimentation and analysis in a multitude of fields. Chromatography is one of the most popular, well-developed, and well-studied methods used to examine the makeup of a mixture. Thus, the improvement of chromatographic procedures directly benefits research across many scientific disciplines. The application of a continuous stationary phase gradient to High-Performance Liquid Chromatography (HPLC) methods has been proposed to improve the separation of complex mixtures that are difficult to achieve with existing separation techniques. By incorporating a gradient stationary phase, analysts will create a more selective mode of separation to improve …

Moderate-Intensity Exercise Improves Mesenteric Arterial Function In Male Uc Davis Type-2 Diabetes Mellitus (Ucd-T2dm) Rats: A Shift In The Relative Importance Of Endothelium-Derived Relaxing Factors (Edrf), Md Rahatullah Razan, Said Amissi, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric …

Pyrazole-Sulfonamide Scaffold Featuring Dual-Tail Strategy As Apoptosis Inducers In Colon Cancer, Amira Khalil, Reham M. M. El Hazek, Nashwa H. Zaher, Hagar E. S. Emam, Marwa G. Elgazzar

Pharmacy

Dual-tail strategy has been successfully utilized in the development of novel carbonic anhydrase IX (CA IX) inhibitors. Herein we adopted this approach in the design and synthesis of a series of novel pyridine sulfonamide-pyrazole hybrid scaffold mimicking dual-tail inhibitors of CA IX. A library of 15 compounds was synthesized and assessed for their potential cytotoxic effects against colorectal cancer cells. Compounds 3, and 11 induced potential cytotoxic effects against the three cancer cell lines (HCT-116, HT-29, and SW-620) with IC₅₀s’ of 45.88, 28.27, and 16.57 uM, 25.01, 8.99, and 3.27 µM, respectively. Both compounds induced cellular apoptosis …

March / April 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the March & April 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …

Amphiphilic Cell-Penetrating Peptides Containing Arginine And Hydrophobic Residues As Protein Delivery Agents, Jonathan Moreno, Khalid Zoghebi, David Salehi, Lois Kim, Sorour Khayyatnejad Shoushtari, Rakesh K. Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The entry of proteins through the cell membrane is challenging, thus limiting their use as potential therapeutics. Seven cell-penetrating peptides, designed in our laboratory, were evaluated for the delivery of proteins. Fmoc solid-phase peptide synthesis was utilized for the synthesis of seven cyclic or hybrid cyclic–linear amphiphilic peptides composed of hydrophobic (tryptophan (W) or 3,3-diphenylalanine (Dip) and positively-charged arginine (R) residues, such as [WR]4, [WR]9, [WWRR]4, [WWRR]5, [(RW)5K](RW)5, [R5K]W7, and [DipR]5. Confocal microscopy was used to screen the peptides as a protein delivery system of model cargo proteins, green and red fluorescein proteins (GFP and RFP). Based on the confocal …

Quantitative Phosphoproteomic Analysis Reveals Unique Camp Signaling Pools Emanating From Ac2 And Ac6 In Human Airway Smooth Muscle Cells, Isabella Cattani-Cavalieri, Yue Li, Jordyn Margolis, Amy S. Bogard, Moom R. Roosan, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Human airway smooth muscle (HASM) is the primary target of ßAR agonists used to control airway hypercontractility in asthma and chronic obstructive pulmonary disease (COPD). ßAR agonists induce the production of cAMP by adenylyl cyclases (ACs), activate PKA and cause bronchodilation. Several other G-protein coupled receptors (GPCR) expressed in human airway smooth muscle cells transduce extracellular signals through cAMP but these receptors elicit different cellular responses. Some G-protein coupled receptors couple to distinct adenylyl cyclases isoforms with different localization, partly explaining this compartmentation, but little is known about the downstream networks that result. We used quantitative phosphoproteomics to define the …

Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and …

Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia

Pharmacy Faculty Articles and Research

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.

Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.

Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI …

Challenging Breast Cancer Through Novel Sulfonamide–Pyridine Hybrids: Design, Synthesis, Carbonic Anhydrase Ix Inhibition And Induction Of Apoptosis., Amira Khalil, Nashwa H. Zaher, Reham Mm Elhazek, Ahmed E. Gouda, Marwa G. Elgazzar

Pharmacy

Background: Among the important key modulators of the tumor microenvironment and hypoxia is a family of enzymes named carbonic anhydrases. Herein, 11 novel sulfonamide–pyridine hybrids (2–12) were designed, synthesized and biologically evaluated for their potential use in targeting breast cancer. Methods & results: The para chloro derivative 7 reported the highest cytotoxic activity against the three breast cancer cell lines used. In addition, compound 7 was found to induce cell cycle arrest and autophagy as well as delaying wound healing. The IC50 of compound 7 against carbonic anhydrase IX was 253 ± 12 nM using dorzolamide HCl as control. Conclusion: …

January / February 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the January & February 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Brivaracetam To Treat Partial Onset Seizures In Adults., Dustin Latimer, David Le, Evan P. Falgoust, Patrick Ingraffia, Alaa Abd-Elsayed, Elyse M. Cornett, Rupin Singh, Joohee Choi, Giustino Varrassi, Adam M. Kaye, Alan D. Kaye, Latha Ganti

School of Pharmacy Faculty Articles

PURPOSE OF REVIEW: Seizures are a hyperexcitable, and hypersynchronous imbalance between excitatory and inhibitory factors (E/I imbalance) in neurotransmission, and epilepsy is the recurrent manifestation of seizures within a reasonable time frame and without being attributable to a reversible cause. Brivaracetam is a derivative of the antiepileptic agent, levetiracetam, that is used as adjuvant therapy for focal onset seizures. It was approved by the FDA in 2016 and has shown promising results with minimal adverse effect reactions in clinical trials.

RECENT FINDINGS: Brivaracetam has been used in multiple clinical trials at various dosages in adults that have partial-onset seizures refractory …