Medicinal and Pharmaceutical Chemistry Commons^™

Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles …

Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation Of Monocytes And Reduces Il-1Β Secretion By Urate Crystal Stimulated Gout Pbmcs, Sandy Elsayed, Gregory D. Jay, Ralph Cabezas, Marwa Qadri, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Objectives

To compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.

Methods

Acute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry. PBMCs were primed with Pam3CSK4 (1μg/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU …

Ketamine As A Treatment Modality For Treatment-Resistant Depression, Tracy Wulff, Shen Cao

Physician Assistant Capstones, 2020-current

Many recent studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to produce antidepressant effects that may be effective in helping reduce treatment-resistant major depression. In particular, three double-blinded randomized control trials have been conducted to assess the viability and effectiveness of this medication for treatment. This systematic literature review will analyze these studies and determine if the overall research indicates that ketamine is useful in improving depression as measured by the Montgomery–Asberg Depression Rating Scale (MADRS)¹.

Objective: Assess the effectiveness of IV Ketamine in reducing treatment-resistant major depressive disorder as measured by the Montgomery–Asberg …

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

Student Scholar Symposium Abstracts and Posters

Molecular extension and dissection techniques are used to design a morphine derivative that promotes selective binding in inflamed tissue due to its lower pH while avoiding dangerous activation in the brain. Morphine is used to treat pain associated with inflammation. While being effective analgesics, opioids carry the risk of central side effects, including addiction, respiratory depression, and sedation. Opioids are agonists that bind to the μ-opioid peptide receptor (MOR) within central and peripheral nerves and act via a G-protein coupled receptor pathway.

Deprotonation of the tertiary amine induces a negative charge on the nitrogen, discouraging binding at physiological pH (pH=7.4). …

Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = …

Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gα_s so it was long assumed that all ACs are activated by Gα_s-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …

Cyclic Peptide-Gadolinium Nanocomplexes As Sirna Delivery Tools, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Dindyal Mandal, David Stickley, Stephanie Nagasawa, Joshua Long, Sandeep Lohan, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)₅C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)₅C]-GdNPs, in the range of 240 to 260 nm upon mixing with an aqueous solution of GdCl₃. Herein, we report [(WR)₅C]-GdNPs as an efficient siRNA delivery system. The peptide-based gadolinium nanoparticles (50 µM) did not exhibit significant cytotoxicity (~93% cell viability at 50 µM) in human leukemia T lymphoblast cells (CCRF-CEM) and triple-negative breast cancer cells (MDA-MB-231) after 48 h. Fluorescence-activated cell sorting (FACS) analysis indicated …

Cyclic Dipeptides: The Biological And Structural Landscape With Special Focus On The Anti-Cancer Proline-Based Scaffold, Joanna Bojarska, Adam Mieczkowski, Zyta M. Ziora, Mariusz Skwarczynski, Istvan Toth, Ahmed O. Shalash, Keykavous Parang, Shaima Ahmed El-Mowafi, Eman H. M. Mohammed, Sherif Elnagdy, Maha Alkhazindar, Wojciech M. Wolf

Pharmacy Faculty Articles and Research

Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the …

A Comparison Of Calcium Aggregation And Ultracentrifugation Methods For The Preparation Of Rat Brain Microsomes For Drug Metabolism Studies, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

Preparation of brain microsomes by the calcium chloride aggregation method has been suggested as an alternative to the ultracentrifugation method. However, the effects of the calcium chloride concentration on the quality of the microsomal fractions are not known. Brain microsomes were prepared from the adult rat brains using the high-speed ultracentrifugation and low-speed calcium chloride (10–100 mM) aggregation methods (n = 5–6 per group). The microsomal protein yield (spectrometry), the cytochrome P450 reductase (CPR) activity (spectrometry), and the monooxygenase activities (UPLC-MS/MS) of CYP2D and CYP2E1 were determined in the obtained fractions. Increasing the concentrations of calcium chloride progressively increased …

Associations Between Varied Susceptibilities To Pfatp4 Inhibitors And Genotypes In Ugandan Plasmodium Falciparum Isolates., Oriana Kreutzfeld, Stephanie A. Rasmussen, Aarti A. Ramanathan, Patrick K. Tumwebaze, Oswald Byaruhanga, Thomas Katairo, Victor Asua, Martin Okitwi, Stephen Orena, Jennifer Legac, Melissa D. Conrad, Samuel L. Nsobya, Ozkan Aydemir, Jeffrey Bailey, Maelle Duffey, Brett R. Bayles, Akhil B. Vaidya, Roland A. Cooper, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda, from 2016 to 2019. Median IC50s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many nonsynonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K …

Proteoglycan-4 Is An Essential Regulator Of Synovial Macrophage Polarization And Inflammatory Macrophage Joint Infiltration, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Tannin A. Schmidt, Jennifer Totonchy, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background

Synovial macrophages perform a multitude of functions that include clearance of cell debris and foreign bodies, tissue immune surveillance, and resolution of inflammation. The functional diversity of macrophages is enabled by distinct subpopulations that express unique surface markers. Proteoglycan-4 (PRG4) is an important regulator of synovial hyperplasia and fibrotic remodeling, and the involvement of macrophages in PRG4’s synovial role is yet to be defined. Our objectives were to study the PRG4’s importance to macrophage homeostatic regulation in the synovium and infiltration of pro-inflammatory macrophages in acute synovitis and investigate whether macrophages mediated synovial fibrosis in Prg4 gene-trap (Prg4 …

Design And Application Of Hybrid Cyclic-Linear Peptide-Doxorubicin Conjugates As A Strategy To Overcome Doxorubicin Resistance And Toxicity, Saghar Mozaffari, David Salehi, Parvin Mahdipoor, Richard Beuttler, Rakesh Tiwari, Hamidreza Montazeri Aliabadi, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is used for breast cancer, leukemia, and lymphoma treatment as an effective chemotherapeutic agent. However, Dox use is restricted due to inherent and acquired resistance and an 8-fold increase in the risk of potentially fatal cardiotoxicity. Hybrid cyclic-linear peptide [R5K]W7A and linear peptide R5KW7A were conjugated with Dox through a glutarate linker to afford [R5K]W7A-Dox and R5KW7A-Dox conjugates to generate Dox derivatives. Alternatively, [R5K]W7C was conjugated with Dox via a disulfide linker to generate [R5K]W7C–S–S-Dox conjugate, where S–S is a disulfide bond. Comparative antiproliferative assays between conjugates [R5K]W7A-Dox, [R5K]W7C–S–S-Dox, linear R5KW7A-Dox, the corresponding physical mixtures of the peptides, …

Subtype-Selective Positive Modulation Of KCa 2 Channels Depends On The Ha/Hb Helices, Young-Woo Nam, Meng Cui, Naglaa Salem, Razan Orfali, Misa Nguyen, Grace Yang, Mohammad Asikur Rahman, Judy Lee, Miao Zhang

Pharmacy Faculty Articles and Research

Background and Purpose

In the activated state of small-conductance Ca2+-activated potassium (KCa 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates KCa 2.2a and KCa 2.3 channel activity but not the KCa 2.1 and KCa 3.1 subtypes.

Experimental Approach

Site-directed mutagenesis, patch-clamp recordings and in silico modeling were utilized to explore the structural determinants for the subtype-selective modulation of KCa 2 channels by CyPPA.

Key Results

Mutating residues in the HA (V420) and HB (K467) helices of KCa 2.2a channels to their equivalent residues in KCa 3.1 channels diminished the potency of CyPPA. CyPPA elicited …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Mcl-1 Inhibition: Managing Malignancy In Multiple Myeloma., Omar Al-Odat, Max Von Suskil, Robert Chitren, Weam Elbezanti, Sandeep Srivastava, Tulin Budak-Alpddogan, Subash C. Jonnalagadda, Bharat Aggarwal, Manoj Pandey

Faculty Scholarship for the College of Science & Mathematics

Multiple myeloma (MM) is a plasma cells neoplasm. The overexpression of Bcl-2 family proteins, particularly myeloid cell leukemia 1 (Mcl-1), plays a critical role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with drug resistance and overall poor prognosis of MM. Thus, inhibition of the Mcl-1 protein considered as a therapeutic strategy to kill the myeloma cells. Over the last decade, the development of selective Mcl-1 inhibitors has seen remarkable advancement. This review presents the critical role of Mcl-1 in the progression of MM, the most prominent BH3 mimetic and semi-BH3 mimetic that selectively inhibit Mcl-1, and …

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction …

Engineering And Characterization Of Human Β-Defensin-3 And Its Analogues And Microcin J25 Peptides Against Mannheimia Haemolytica And Bovine Neutrophils, Harpreet Dhingra, Kamaljit Kaur, Baljit Singh

Pharmacy Faculty Articles and Research

Mannheimia haemolytica-induced bovine respiratory disease causes loss of millions of dollars to Canadian cattle industry. Current antimicrobials are proving to be ineffective and leave residues in meat. Antimicrobial peptides (AMPs) may be effective against M. haemolytica while minimizing the risk of drug residues. Cationic AMPs can kill bacteria through interactions with the anionic bacterial membrane. Human β-Defensin 3 (HBD3) and microcin J25 (MccJ25) are AMPs with potent activity against many Gram-negative bacteria. We tested the microbicidal activity of wild-type HBD3, three HBD3 peptide analogues (28 amino acid, 20AA, and 10AA) derived from the sequence of natural HBD3, and MccJ25 …

Evaluation Of A Keratin 1 Targeting Peptide-Doxorubicin Conjugate In A Mouse Model Of Triple-Negative Breast Cancer, Azam Saghaeidehkordi, Shiuan Chen, Sun Yang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), a subtype of breast cancer that is aggressive with a poor prognosis. While chemotherapeutics are potent, these agents lack specificity and are equally toxic to cancer and nonmalignant cells and tissues. Targeted therapies for TNBC treatment could lead to more safe and efficacious drugs. We previously engineered a breast cancer cell targeting peptide 18-4 that specifically binds cell surface receptor keratin 1 (K1) on breast cancer cells. A conjugate of peptide 18-4 and doxorubicin (Dox) containing an acid-sensitive hydrazone linker showed specific toxicity toward TNBC cells. Here, we report the …

Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca²⁺ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca²⁺ transients, but did not affect Ca²⁺ transients induced by high K^{+ …}

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

Student Scholar Symposium Abstracts and Posters

Opioids such as morphine are important pain-relieving drugs but also carry a risk of harmful side effects including addiction. Morphine is active in both healthy and inflamed tissue, however, decreasing the pKa of the biochemically-active amine group can promote selective binding in the more acidic conditions of inflamed tissue and reduce harmful side effects associated with opioids. Herein, we explore the impact of fluorination on the pKa of fluoromorphine derivatives to identify which will bind selectively in inflamed tissue. Theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔGaq" …

Measuring The Decrement Times Of Volatile Anesthetics In Drosophila Melanogaster Using Gas Chromatography-Mass Spectrometry, Jason Tolley

Honors Program Projects

Background

Model organisms are widely used in research, especially in the context of complex situations. One model organism that has been widely used is the common fruit fly, Drosophila melanogaster (D. mel). D. mel are most commonly used in the context of genetics, but they have also been widely used in research focusing on general anesthetics. One value that has not been measured in D. mel, however, as it relates to general anesthetics, is the decrement times. This is what was the present research set out to determine.

Methods

The anesthetics studied in this research were isoflurane …

Compounded Gabapentin For Felines: Associated Metabolic Processes And Analysis Of Potency, Johnny Altwal

Student Scholar Symposium Abstracts and Posters

Pharmaceutical compounding provides pharmacists and clinicians the opportunity to create unique drug formulations that are better suited to a specific patient’s needs. This is especially prevalent in veterinary medicine where clinicians treat a variety of maladies in a large number of species, thereby requiring unique formulations to more easily deliver drugs to animals. Several examples of compounded veterinary formulations with sub-therapeutic potencies have been published, but none examine compounded gabapentin. Gabapentin is frequently compounded into an oral suspension for veterinary use from tablets or capsules for the purpose of pain management in felines and other small animals. The project’s goals …

Suppression Of Human Coronavirus 229e Infection In Lung Fibroblast Cells Via Rna Interference, Hamidreza Montazeri Aliabadi, Jennifer Totonchy, Parvin Mahdipoor, Keykavous Parang, Hasan Uludağ

Pharmacy Faculty Articles and Research

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will …

Ciliary Extracellular Vesicles Are Distinct From The Cytosolic Extracellular Vesicles, Ashraf M. Mohieldin, Rajasekharreddy Pala, Richard Beuttler, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Extracellular vesicles (EVs) are cell‐derived membrane vesicles that are released into the extracellular space. EVs encapsulate key proteins and mediate intercellular signalling pathways. Recently, primary cilia have been shown to release EVs under fluid‐shear flow, but many proteins encapsulated in these vesicles have never been identified. Primary cilia are ubiquitous mechanosensory organelles that protrude from the apical surface of almost all human cells. Primary cilia also serve as compartments for signalling pathways, and their defects have been associated with a wide range of human genetic diseases called ciliopathies. To better understand the mechanism of ciliopathies, it is imperative to know …

Categorization Of Marketed Artificial Tear Formulations Based On Their Ingredients: A Rational Approach For Their Use, Avani Kathuria, Kiumars Shamloo, Vishal Jhanji, Ajay Sharma

Pharmacy Faculty Articles and Research

Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations contain a variety of active ingredients, biologically active excipients, and preservatives. Many of these formulations are also available as preservative-free. This study was conducted to inspect artificial tear formulations currently marketed in the United States for their active ingredients, biologically relevant excipients, and preservatives. The marketed artificial tears were examined at various US retail pharmacy chains and using the manufacturers’ website to compile information about active ingredients, inactive ingredients, and …

Anti‑Estrogenic And Anti‑Aromatase Activities Of Citrus Peels Major Compounds In Breast Cancer, Maha Salama, Dina Mahmoud Elkersh, Shahira M. Ezzat, Yasmeen Attiaa, Engy A. Mahrous, Mohey Elmazar

Pharmacy

Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling …

Stability Evaluation Of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect Of Solvents And Storage Conditions, Christopher Ross, Basir Syed, Joanna Pak, Vishal Jhanji, Jason Yamaki, Ajay Sharma

Pharmacy Faculty Articles and Research

Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus keratitis and other ocular infections. Vancomycin ophthalmic drops are not commercially available and require compounding. The present study was designed to investigate the stability of vancomycin ophthalmic drops in normal saline, phosphate-buffered saline (PBS), and balanced salt solution (BSS) while stored at room temperature or under refrigeration. Vancomycin ophthalmic drops (50 mg/mL) were aseptically prepared from commercially available intravenous powder using PBS, BSS, and saline. Solutions were stored at room temperature and in a refrigerator for 28 days. The vancomycin stability was tested by a microbiology assay and high-performance liquid …

Sars-Cov-2 Early Infection Signature Identified Potential Key Infection Mechanisms And Drug Targets, Yue Li, Ashley Duche, Michael R. Sayer, Don Roosan, Farid G. Khalafalla, Rennolds S. Ostrom, Jennifer Totonchy, Moom Roosan

Pharmacy Faculty Articles and Research

Background

The ongoing COVID-19 outbreak has caused devastating mortality and posed a significant threat to public health worldwide. Despite the severity of this illness and 2.3 million worldwide deaths, the disease mechanism is mostly unknown. Previous studies that characterized differential gene expression due to SARS-CoV-2 infection lacked robust validation. Although vaccines are now available, effective treatment options are still out of reach.

Results

To characterize the transcriptional activity of SARS-CoV-2 infection, a gene signature consisting of 25 genes was generated using a publicly available RNA-Sequencing (RNA-Seq) dataset of cultured cells infected with SARS-CoV-2. The signature estimated infection level accurately in …

Repurposing Of Omarigliptin As A Neuroprotective Agent Based On Docking With A2a Adenosine And Ache Receptors, Brain Glp-1 Response And Its Brain/Plasma Concentration Ratio After 28 Days Multiple Doses In Rats Using Lc-Ms/Ms, Bassam Ayoub, Haidy Michel, Shereen Mowaka, Moataz S. Hendy, Mariam M. Tadros

Pharmacy

Abstract: The authors in the current work suggested the potential repurposing of omarigliptin (OMR) for neurodegenerative diseases based on three new findings that support the preliminary finding of crossing BBB after a single dose study in the literature. The first finding is the positive results of the docking study with the crystal structures of A2A adenosine (A2AAR) and acetylcholine esterase (AChE) receptors. A2AAR is a member of non-dopaminergic GPCR superfamily receptor proteins and has essential role in regulation of glutamate and dopamine release in Parkinson’s disease while AChE plays a major role in Alzheimer’s disease as the primary enzyme responsible …

Label‑Free Spectral Imaging To Study Drug Distribution And Metabolism In Single Living Cells, Qamar Alshammari, Rajasekharreddy Pala, Nir Katzir, Surya M. Nauli

Pharmacy Faculty Articles and Research

During drug development, evaluation of drug and its metabolite is an essential process to understand drug activity, stability, toxicity and distribution. Liquid chromatography (LC) coupled with mass spectrometry (MS) has become the standard analytical tool for screening and identifying drug metabolites. Unlike LC/MS approach requiring liquifying the biological samples, we showed that spectral imaging (or spectral microscopy) could provide high-resolution images of doxorubicin (dox) and its metabolite doxorubicinol (dox’ol) in single living cells. Using this new method, we performed measurements without destroying the biological samples. We calculated the rate constant of dox translocating from extracellular moiety into the cell and …