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Articles 1 - 30 of 633

Full-Text Articles in Medicinal and Pharmaceutical Chemistry

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang Jul 2022

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several classes of ...


Jatropha Tanjorensis A Flora Of Southeast Nigeria: Isolation And Characterization Of Naringenin And Validation Of Bio-Enhanced Synergistical Activity Of Α- Tocopherol Toward Clinical Isolates Of Resistant Bacterial, Ikechukwu Kingsley Ijoma, Vincent Ishmael Egbulefu Ajiwe Jun 2022

Jatropha Tanjorensis A Flora Of Southeast Nigeria: Isolation And Characterization Of Naringenin And Validation Of Bio-Enhanced Synergistical Activity Of Α- Tocopherol Toward Clinical Isolates Of Resistant Bacterial, Ikechukwu Kingsley Ijoma, Vincent Ishmael Egbulefu Ajiwe

Makara Journal of Science

Jatropha tanjorensis is among the rich floras of Southeast Nigeria and used by ethnic people to treat infections and manage health conditions. Ethnomedicine has long been employed in the treatment of ailments caused by bacterial pathogens. Studies showed that the incorporation of synthetic α-tocopherol to an antibacterial agent improves its activity. However, knowledge about the antibacterial-enhanced activity of plant-based α-tocopherols, especially those isolated from Jatropha tanjorensis, is limited because of the different bioactivities of synthetic and natural α-tocopherols. To determine the phytochemicals in J. tanjorensis, we carried out the structural elucidation of its leaf extracts. Naringenin and α-tocopherol were identified ...


Channelopathy Of Small- And Intermediate-Conductance Ca2+-Activated K+ Channels, Young-Woo Nam, Myles Downey, Mohammad Asikur Rahman, Meng Cui, Miao Zhang Jun 2022

Channelopathy Of Small- And Intermediate-Conductance Ca2+-Activated K+ Channels, Young-Woo Nam, Myles Downey, Mohammad Asikur Rahman, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca2+-activated K+ (KCa2.x/KCa3.1 also called SK/IK) channels are gated exclusively by intracellular Ca2+. The Ca2+ binding protein calmodulin confers sub-micromolar Ca2+ sensitivity to the channel-calmodulin complex. The calmodulin C-lobe is constitutively associated with the proximal C-terminus of the channel. Interactions between calmodulin N-lobe and the channel S4-S5 linker are Ca2+-dependent, which subsequently trigger conformational changes in the channel pore and open the gate. KCNN genes encode four subtypes, including KCNN1 for KCa2.1 (SK1), KCNN2 for KCa2.2 ...


Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg Jun 2022

Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg

All Faculty Scholarship for the College of the Sciences

C-fused γ-lactam-lactones are resident in several bioactive molecules, including anticancer agents such as omuralide. In this embodiment, we report mild conditions for the catalytic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids. The use of dichloromethane as the solvent and Ph3PS as the catalyst led to predominant 6-endo-trig cyclization and furnished the trans-fused-γ-lactam-δ-lactones. The transformation is modular, regioselective, chemoselective, and diastereoselective. The γ-lactam-δ-lactones bear angular quaternary benzylic stereocenters, which is noteworthy since the presence of a quaternary carbon in bioactive small molecules often promotes an element of conformational restriction that imparts potency, selectivity, and metabolic stability. The ...


Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria May 2022

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of ...


Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed May 2022

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 ...


Integration Of Medicinal Fungi Into The Heber W. Youngken Jr. Medicinal Garden, Anthony Makashov May 2022

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 ...


Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Matthew Gartner May 2022

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 ...


Multimodal Approach To Chronic Pain Management And Prevention Of Opioid Use Disorder, Hannah Elston May 2022

Multimodal Approach To Chronic Pain Management And Prevention Of Opioid Use Disorder, Hannah Elston

The Eleanor Mann School of Nursing Undergraduate Honors Theses

Background. Chronic pain (CP) is a major public health problem that affects one-third of the population and can interfere with the activities of daily life and cause decreased quality of life. Patients with CP have been increasingly prescribed opioids, contributing to the rise in the opioid epidemic. Due to the long-term nature of CP, the use of opioids as the sole treatment for CP can cause tolerance and increased dosages overtime which can lead to addiction and potentially overdose. Therefore, CP treatment should include multimodal approaches to treatment to prevent opioid misuse, opioid use disorder (OUD), and overdose. Multimodal treatments ...


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 Apr 2022

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 ...


Bis-Cinnamamide Derivatives As Ape/Ref-1 Inhibitors For The Treatment Of Human Melanoma, Razan Alhazmi, Shirley Tong, Shaban Darwish, Elina Khanjani, Bharti Khungar, Swati Chawla, Zhonghui Zheng, Richard Chamberlain, Keykavous Parang, Sun Yang Apr 2022

Bis-Cinnamamide Derivatives As Ape/Ref-1 Inhibitors For The Treatment Of Human Melanoma, Razan Alhazmi, Shirley Tong, Shaban Darwish, Elina Khanjani, Bharti Khungar, Swati Chawla, Zhonghui Zheng, Richard Chamberlain, Keykavous Parang, Sun Yang

Pharmacy Faculty Articles and Research

Human malignant melanoma exhibits imbalances in redox status, leading to activation of many redox-sensitive signaling pathways. APE/Ref-1 is a multifunctional protein that serves as a redox chaperone that regulates many nuclear transcription factors and is an important mechanism in cancer cell survival of oxidative stress. Previous studies showed that APE/Ref-1 is a potential druggable target for melanoma therapy. In this study, we synthesized a novel APE/Ref-1 inhibitor, bis-cinnamoyl-1,12-dodecamethylenediamine (2). In a xenograft mouse model, compound 2 treatment (5 mg/kg) significantly inhibited tumor growth compared to the control group, with no significant systemic toxicity observed. We ...


The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez Apr 2022

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with ...


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 Apr 2022

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 ...


Iron Effects On Clostridioides Difficile Toxin Production And Antimicrobial Susceptibilities, Jason Yamaki, Swati Chawla, Shirley Tong, Kate Alison Lozada, Sun Yang Apr 2022

Iron Effects On Clostridioides Difficile Toxin Production And Antimicrobial Susceptibilities, Jason Yamaki, Swati Chawla, Shirley Tong, Kate Alison Lozada, Sun Yang

Pharmacy Faculty Articles and Research

Despite the benefits of red blood cell (RBC) transfusion therapy, it can render patients vulnerable to iron overload. The excess iron deposits in various body tissues cause severe complications and organ damage such as cardiotoxicity and mold infections. Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea among cancer patients and is associated with significant morbidity and mortality. Our study aims to determine the role of iron overload and the effects of iron chelators on CDI. Our results demonstrated that iron (Fe3+) stimulated the growth of C. difficile with increased colony formation units (CFU) in a ...


Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides As Promising Agents For Sirna Delivery, Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari Apr 2022

Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides As Promising Agents For Sirna Delivery, Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Recent approvals of siRNA-based products motivated the scientific community to explore siRNA as a treatment option for several intractable ailments, especially cancer. The success of approved siRNA therapy requires a suitable and safer drug delivery agent. Herein, we report a series of oleyl conjugated histidine–arginine peptides as a promising nonviral siRNA delivery tool. The conjugated peptides were found to bind with the siRNA at N/P ratio ≥ 2 and demonstrated complete protection for the siRNA from early enzymatic degradation at N/P ratio ≥ 20. Oleyl-conjugated peptide -siRNA complexes were found to be noncytotoxic in breast cancer cells (MCF-7 and ...


Quadruped Gait And Regulation Of Apoptotic Factors In Tibiofemoral Joints Following Intra-Articular Rhprg4 Injection In Prg4 Null Mice, Daniel S. Yang, Edward E. Dickerson, Ling X. Zhang, Holly Richendrfer, Padmini N. Karamchedu, Gary A. Badger, Tannin A. Schmidt, Alger M. Fredericks, Khaled A. Elsaid, Gregory D. Jay Apr 2022

Quadruped Gait And Regulation Of Apoptotic Factors In Tibiofemoral Joints Following Intra-Articular Rhprg4 Injection In Prg4 Null Mice, Daniel S. Yang, Edward E. Dickerson, Ling X. Zhang, Holly Richendrfer, Padmini N. Karamchedu, Gary A. Badger, Tannin A. Schmidt, Alger M. Fredericks, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4—PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4−/− (N = 44) mice of both sexes were injected with rhPRG4 and ...


Acetaminophen, A Therapeutic Or An Extremely Toxic Remedy – A Review, Genica Caragea, Oana Avram, Andreea Pauna, Andreea Cristina Costea, Miruna Tudosie Apr 2022

Acetaminophen, A Therapeutic Or An Extremely Toxic Remedy – A Review, Genica Caragea, Oana Avram, Andreea Pauna, Andreea Cristina Costea, Miruna Tudosie

Journal of Mind and Medical Sciences

When a new coronavirus appeared in the late 2019, identified as the cause of several cases of pneumonia in Wuhan, Paracetamol was initially reported to be the preferable antipyretic medication, choice which was detrimental to the use of other drugs. People have resorted to buying large stocks of Paracetamol and some have used it in large doses, regardless of the consequences. However, the Paracetamol (Acetaminophen) overdose remains the leading cause of death or transplantation due to acute liver failure in many parts of the world. This review aims at presenting the pharmacokinetics, the clinical signs, and the risk factors for ...


The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen Apr 2022

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen

CSBSJU Distinguished Thesis

An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be ...


Prenatal Drug Exposure And Its Effects On Fetal Development: Clinical And Health Education Implications, Johanna Marie Olo Tapangan Apr 2022

Prenatal Drug Exposure And Its Effects On Fetal Development: Clinical And Health Education Implications, Johanna Marie Olo Tapangan

Senior Honors Theses

Prenatal drug exposure is a common clinical phenomenon in pregnancy cases. Pregnancy is a fragile period of time for both the mother and the fetus. Therefore, strict drug regulation is important to ensure the safety and wellbeing of the developing fetus. Certain drugs, once thought to be safe, have been found to have detrimental effects on the normal development of functioning organ systems in the fetus. Current research has identified drugs that when taken during pregnancy can result in the onset of fetal physical abnormalities, impaired brain development, and disrupted organogenesis and organ function. Thalidomide, losartan, opioids, alcohol, and caffeine ...


Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen Apr 2022

Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen

CSBSJU Distinguished Thesis

Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has ...


Antiviral Drug Development: Targeted Design And Broad Spectrum Approach, Claude Krummenacher Mar 2022

Antiviral Drug Development: Targeted Design And Broad Spectrum Approach, Claude Krummenacher

Faculty Scholarship for the College of Science & Mathematics

No abstract provided.


Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Agents, David Salehi, Saghar Mozaffari, Khalid Zoghebi, Sandeep Lohan, Dindyal Mandal, Rakesh Tiwari, Keykavous Parang Mar 2022

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Agents, David Salehi, Saghar Mozaffari, Khalid Zoghebi, Sandeep Lohan, Dindyal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of cyclic peptides, [(DipR)(WR)4], [(DipR)2(WR)3], [(DipR)3(WR)2], [(DipR)4(WR)], and [DipR]5, and their linear counterparts containing arginine (R) as positively charged residues and tryptophan (W) or diphenylalanine (Dip) as hydrophobic residues, were synthesized and evaluated for their molecular transporter efficiency. The in vitro cytotoxicity of the synthesized peptides was determined in human epithelial ovary adenocarcinoma cells (SK-OV-3), human lymphoblast peripheral blood cells (CCRF-CEM), human embryonic epithelial kidney healthy cells (HEK-293), human epithelial mammary gland adenocarcinoma cells (MDA-MB-468), pig epithelial kidney normal cells (LLC-PK1), and human epithelial fibroblast uterine sarcoma ...


Combination Of Amphiphilic Cyclic Peptide [R4W4] And Levofloxacin Against Multidrug-Resistant Bacteria, Muhammad Imran Sajid, Sandeep Lohan, Shun Kato, Rakesh Kumar Tiwari Mar 2022

Combination Of Amphiphilic Cyclic Peptide [R4W4] And Levofloxacin Against Multidrug-Resistant Bacteria, Muhammad Imran Sajid, Sandeep Lohan, Shun Kato, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Bacterial resistance is a growing global concern necessitating the discovery and development of antibiotics effective against the drug-resistant bacterial strain. Previously, we reported a cyclic antimicrobial peptide [R4W4] containing arginine (R) and tryptophan (W) with a MIC of 2.67 µg/mL (1.95 µM) against methicillin-resistant Staphylococcus aureus (MRSA). Herein, we investigated the cyclic peptides [R4W4] or linear (R4W4) and their conjugates (covalent or noncovalent) with levofloxacin (Levo) with the intent to improve their potency to target drug-resistant bacteria. The physical mixture of the Levo with the cyclic [R4 ...


Daclizumab (Zinbryta®): An Emerging Therapy For The Treatment Of Relapsing-Remitting Multiple Sclerosis, Morgan Homan, Sunitha Jones, Michaela Louden, Molly Wheeler, Anh Dao Le, Lindsey Peters Mar 2022

Daclizumab (Zinbryta®): An Emerging Therapy For The Treatment Of Relapsing-Remitting Multiple Sclerosis, Morgan Homan, Sunitha Jones, Michaela Louden, Molly Wheeler, Anh Dao Le, Lindsey Peters

Pharmacy and Wellness Review

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by the deterioration of the myelin sheath, causing axonal damage which leads to debilitating symptoms. Most therapies for the treatment of MS, including daclizumab, primarily target relapsing-remitting multiple sclerosis (RRMS), a form of MS where patients experience periods of exacerbated symptoms as well as intermittent periods of remission. Daclizumab is a humanized monoclonal antibody that is administered as a once monthly subcutaneous injection. The SELECT trilogy of trials have been instrumental in providing safety and efficacy data for daclizumab. The DECIDE study was the first randomized controlled ...


An Atypical Case Of Extreme Polypharmacy, Michael A. Veronin Mar 2022

An Atypical Case Of Extreme Polypharmacy, Michael A. Veronin

Pharmacy Faculty Publications and Presentations

A commonly reported definition of polypharmacy is the numerical definition of 5 or more medications daily, and definitions have ranged from 2 or more to 11 or more medications. In this case report, an extreme case of polypharmacy is presented, highlighted by the inordinate number of drugs used over time throughout the patient’s care. A 48-year-old African American female with multiple comorbidities experienced a serious adverse drug event (ADE) prompting reporting to MedWatch, the US Food and Drug Administration’s adverse drug event reporting system. The patient’s concomitant medications included 146 drug entities, across 82 therapeutic drug categories ...


Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov Mar 2022

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov

Chemistry & Biochemistry Faculty Publications

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds ...


Late-Stage Chemoenzymatic Installation Of Hydroxy-Bearing Allyl Moiety On The Indole Ring Of Tryptophan-Containing Peptides, Nagaraju Mupparapu, Lauren Brewster, Katrina F. Ostrom, Sherif I. Elshahawi Feb 2022

Late-Stage Chemoenzymatic Installation Of Hydroxy-Bearing Allyl Moiety On The Indole Ring Of Tryptophan-Containing Peptides, Nagaraju Mupparapu, Lauren Brewster, Katrina F. Ostrom, Sherif I. Elshahawi

Pharmacy Faculty Articles and Research

The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification and leads to changes in their biological properties. Here, the synthesis of two hydroxy-bearing allyl pyrophosphates is described. A chemoenzymatic method is demonstrated which uses a promiscuous indole prenyltransferase enzyme to install a dual reactive hydroxy-bearing allyl moiety directly on the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.


“Hiccups” With Covid-19 Management, Yong W. Lee, Jacob Psomiadis, Sarah Akbani, Marvin Lopez-Medal, Aisha Miller Feb 2022

“Hiccups” With Covid-19 Management, Yong W. Lee, Jacob Psomiadis, Sarah Akbani, Marvin Lopez-Medal, Aisha Miller

Advances in Clinical Medical Research and Healthcare Delivery

Hiccups, medically referred as singultus, is a condition that results from involuntary contraction of the diaphragm and intercostal muscles. Singultus is usually a self-limiting condition which typically lasts less than 48 hours but in rare cases, can persist greater than 48 hours. This is a case of a 48 year-old male who was prescribed dexamethasone for COVID-19 but developed intractable singultus for two weeks. Patient was unable to tolerate diet due to intractable singultus leading to vomiting. He underwent various non-pharmacological maneuvers and pharmacotherapy without resolution. Dexamethasone- induced hiccups have been reported as an under recognized side effect of dexamethasone ...


Inhibition Of Interferon-Gamma-Stimulated Melanoma Progression By Targeting Neuronal Nitric Oxide Synthase (Nnos), Shirley Tong, Maris A. Cinelli, Naglaa Salem El-Sayed, He Huang, Anika Patel, Richard B. Silverman, Sun Yang Feb 2022

Inhibition Of Interferon-Gamma-Stimulated Melanoma Progression By Targeting Neuronal Nitric Oxide Synthase (Nnos), Shirley Tong, Maris A. Cinelli, Naglaa Salem El-Sayed, He Huang, Anika Patel, Richard B. Silverman, Sun Yang

Pharmacy Faculty Articles and Research

Interferon-gamma (IFN-γ) is shown to stimulate melanoma development and progression. However, the underlying mechanism has not been completely defined. Our study aimed to determine the role of neuronal nitric oxide synthase (nNOS)-mediated signaling in IFN-γ-stimulated melanoma progression and the anti-melanoma effects of novel nNOS inhibitors. Our study shows that IFN-γ markedly induced the expression levels of nNOS in melanoma cells associated with increased intracellular nitric oxide (NO) levels. Co-treatment with novel nNOS inhibitors effectively alleviated IFN-γ-activated STAT1/3. Further, reverse phase protein array (RPPA) analysis demonstrated that IFN-γ induced the expression of HIF1α, c-Myc, and programmed death-ligand 1 (PD-L1 ...


A Pdk-1 Allosteric Agonist Neutralizes Insulin Signaling Derangements And Beta-Amyloid Toxicity In Neuronal Cells And In Vitro, Henry Querfurth, John Marshall, Keykavous Parang, Mengia S. Rioult-Pedotti, Rakesh Tiwari, Bumsup Kwon, Steve Reisinger, Han-Kyu Lee Jan 2022

A Pdk-1 Allosteric Agonist Neutralizes Insulin Signaling Derangements And Beta-Amyloid Toxicity In Neuronal Cells And In Vitro, Henry Querfurth, John Marshall, Keykavous Parang, Mengia S. Rioult-Pedotti, Rakesh Tiwari, Bumsup Kwon, Steve Reisinger, Han-Kyu Lee

Pharmacy Faculty Articles and Research

The Alzheimer’s brain is affected by multiple pathophysiological processes, which include a unique, organ-specific form of insulin resistance that begins early in its course. An additional complexity arises from the four-fold risk of Alzheimer’s Disease (AD) in type 2 diabetics, however there is no definitive proof of causation. Several strategies to improve brain insulin signaling have been proposed and some have been clinically tested. We report findings on a small allosteric molecule that reverses several indices of insulin insensitivity in both cell culture and in vitro models of AD that emphasize the intracellular accumulation of β-amyloid (Aβi). PS48 ...