Pharmaceutics and Drug Design Commons^™

Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]₄ and c[WR]₅ consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in the …

Potential Risk Factors For Mortality Due To Cardiovascular Disease Among Hemodialysed Patients In Indonesia, Diana Laila Ramatillah, Syed Azhar Syed Sulaiman, Kashif Ullah Khan

Pharmaceutical Sciences and Research

Severe vascular calcifications, alterations in cardiovascular structure and function, immune dysfunction, and anemia are adverse effects of parathyroid hormone (PTH), which may contribute to increase risk factors of cardiovascular morbidity and mortality among renal failure patients. To evaluate the potential risk factors for mortality due to cardiovascular disease among hemodialysed patients in Indonesia, this cohort study was conducted. This study included 178 patients on hemodialysis who had been followed up two times a week for nine months (prospective cohort) and 185 patients who died in the last five years (retrospective cohort). Universal sampling technique were used to select the study …

Antioxidant And Elastase Inhibitor Potential Of Petals And Receptacle Of Rose Flower (Rosa Damascena), Evi Mawarni, Chrismis Novalinda Ginting, Linda Chiuman, Ermi Girsang, Rr. Anisa Siwianti Handayani, Wahyu Widowati

Pharmaceutical Sciences and Research

Free radicals can cause damage to cells or tissues, autoimmune diseases, degenerative diseases, or cancer. Therefore, the body needs important substances, namely antioxidants that can help protect the body by reducing negative effect from free radicals. Rose flower (Rosa damascena) has anthocyanin pigment which belongs to flavonoid group which has a function as antioxidant or free radical scavenger. This study aims to determine antioxidant and anti-elastase potentials of rose petals and receptacles. The method used in this study was a qualitative phytochemical test to determine the compounds contained in the Rose Petal Extract (RPE) and Rose Receptacle Extract (RRE), ABTS …

Epigenetic Diet To Modulate Immune Response Against Sars-Cov-2, Andika Andika, Risa Ahdyani, Linda Erlina, Azminah Azminah, Arry Yanuar

Pharmaceutical Sciences and Research

The COVID-19 pandemic has spread to various parts of the world and caused many deaths. The victims are infected by SARS-CoV-2, a new type of coronavirus that has appeared since December 2019 and caused respiratory symptoms, fever, coughing, and shortness of breath. In addition to social distancing, wearing masks and washing hands, diet is important as a defense of the body against SARS-CoV-2. In this review, researchers conducted epigenetic diet studies that could potentially inhibit SARS-CoV-2, and can be consumed and used on a daily basis.

Antagonistic Drug-Herb Interactions Between Clinacanthus Nutans And Cyclophosphamide On Wrl 68 Cell Line, Nurliana Abd Mutalib, Normala Abd Latip

Pharmaceutical Sciences and Research

Clinacanthus nutans (Acanthaceae), locally known as Sabah snake grass, is popularly taken as prevention as well as treatment for cancer in Malaysia, despite lack of concrete clinical evidence. However, it is crucial to evaluate potential antagonistic, additive, or synergistic interactions that may result from the co-treatment of this plant in chemotherapy. In this study, we demonstrate the drug-herb interaction using combination treatment of C. nutans extracts and cyclophosphamide on the WRL 68 cell line. Materials and Methods: Aqueous and 70% ethanol extract of C. nutans leaves were prepared using decoction and maceration methods. MTT assay was used to test …

A Study On The Formulation Of Plant Matrix Tablets From Coarse Botanical Materials Using Cinnamon Bark And Areca Nut As The Model Botanical Materials, Natalia Veronica, Xiu Hui Ang, Shing Ming Ooi, Celine Valeria Liew, Paul Wan Sia Heng

Pharmaceutical Sciences and Research

Background: There is much interest in formulating botanical materials into tablets due to the compactness and ease of administration. However, tableting of coarse milled botanical materials poses a challenge due to poor tableting properties. Objective: To evaluate the feasibility of wet granulation to produce tablets from coarse milled botanical materials and to assess the effect of formulation on properties of the tablets. Materials and Methods: Cinnamon bark and areca nut were milled to obtain 1–2 mm particle size, which was subsequently used in wet granulation using maltodextrin solution as a granulating liquid. Two diluents were tried; microcrystalline …

Long-Lasting, Patient-Controlled, Procedure-Free Contraception: A Review Of Annovera With A Pharmacist Perspective, Jennifer J. Virro, Kathleen Besinque, Christiane E. Carney, Danielle Gross, Brian Bernick, Sebastian Mirkin

Pharmacy Faculty Articles and Research

Annovera (segesterone acetate and ethinyl estradiol vaginal system) is a US Food and Drug Administration FDA-approved long-lasting, reversible contraceptive that is fully administered by the user and does not require a procedure for insertion or removal. The vaginal system is in the shape of a ring and contains low doses of a novel progestin, egesterone acetate, and ethinyl estradiol. It is made of silicone and is fully pliable and flexible. The vaginal system is reusable for 13 cycles, using a 21 days in/7 days out regimen, providing women with the ability to control their fertility. Particularly now during the COVID-19 …

The Potential Roles Of Jamu For Covid-19: A Learn From The Traditional Chinese Medicine, Dwi Hartanti, Binar Asrining Dhiani, Shintia Lintang Charisma, Retno Wahyuningrum

Pharmaceutical Sciences and Research

As the pandemic of the coronavirus disease 2019 (COVID-19) continues while there is no drug and vaccine available, every effort to discover one should be considered. This review aimed to discuss the potential use of jamu, the Indonesian traditional herbal medicine, to deal with COVID-19 by following those of more-established traditional Chinese medicine (TCM). The online literature search using the PubMed database, as well as the circulars from the Indonesian Ministry of Health, were carried out to collect data up to June 07, 2020. The use of TCM for the treatment and prevention of COVID-19 has been officiated in the …

Remdesivir: Mechanism And Effectiveness For Coronavirus Disease 2019 (Covid-19), Vina Neldi, Suharjono Suharjono

Pharmaceutical Sciences and Research

Currently, coronavirus disease 2019 (COVID-19) is a very serious health problem. The World Health Organization (WHO) has characterized this disease as a pandemic. Recommendations related to vaccines and drugs are not available yet because they are still in the clinical trial phase, and one of the superior drugs is remdesivir which has an antiviral activity. Several clinical trials of this drug are being carried out with the aim of evaluating its safety and efficacy in COVID-19 patients. There are two clinical trials with completed recruitment status, which are NCT04257656 and NCT04280705. NCT04257656 showed that remdesivir had faster time for clinical …

A Mini Review : Clinically Significant Potential Drug-Drug Interactions In Covid-19 And Comorbid Therapy, Ana Khusnul Faizah, Nani Wijayanti Dyah Nurrahman, Oki Nugraha Putra

Pharmaceutical Sciences and Research

Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can be aggravated by comorbid diseases. In administering COVID-19 therapy, we need to consider potential drug-drug interactions (pDDIs) with comorbid drugs. Most patients with comorbid diseases get polypharmacy, therefore the risk of pDDIs increases. Potential drug-drug interactions can cause unwanted effects such as toxicity to death. There is no on-label therapy for COVID-19 but FDA has Emergency Use Authorization (EUA) for hydroxychloroquine, chloroquine, azithromycin, remdesivir, ritonavir, and lopinavir. Some COVID-19 treatment potential drug-drug interactions have a level of severity C and D, so …

Sars-Cov-2: Virology And Drug Repurposing Approaches, Ratika Rahmasari, Heri Setiawan, Rezi Riadhi Syahdi, Ayun Arifianti, Marina Ika Irianti, Rani Sauriasari, Juliann Nzembi Makau, Muhareva Raekiansyah

Pharmaceutical Sciences and Research

An emerging coronavirus, SARS-CoV-2, is the causative agent for the ongoing pandemic of coronavirus disease 2019 (COVID-19), which has caused a worldwide social and economic disruption. Currently, no antiviral drugs with proven clinical efficacy, or vaccines for its prevention. Therefore, to combat the pandemic of this novel coronavirus, new effective treatments are urgently needed. In the process of traditional drug development, developing new drugs from scratch is a time- consuming process, requires high-investment, and is a high-risk process, which is impractical to face the immediate global challenge of the SARS-CoV-2 pandemic. Drug repurposing strategy is one of the effective ways …

Chloroquine: An Old To Be Repurposed Drug For Covid-19 Infection (Risk And Benefit), Oki Nugraha Putra, Ana Khusnul Faizah, Nani Wijayanti Dyah Nurrahman, Hardiyono Hardiyono

Pharmaceutical Sciences and Research

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) with a high rate of mortality. Chloroquine and hydroxychloroquine have been used for antimalarial and autoimmune diseases for many years. Due to low toxicity and well tolerability as well as immunomodulatory properties, these drugs are proposed to treat viral infection. Some studies, both in vitro and in a clinical setting, have been evaluated for their ability to treat SARS- CoV-2 as promising therapies. Although The National Agency of Drugs and Food Control of The Republic of Indonesia issued emergency authorization for chloroquine and hydroxychloroquine to be used against …

Prediction Of Asiatic Acid Derivatives Affinity Against Sars-Cov-2 Main Protease Using Molecular Docking, Ida Musfiroh, Alia Resti Azura, Driyanti Rahayu

Pharmaceutical Sciences and Research

COVID-19 is a pandemic that currently occurs in almost all parts of the world, caused by a new coronavirus species that can infect humans, namely SARS-CoV-2. To date, there is no effective drug to treat COVID-19. There are studies proving that the secondary metabolites of pentacyclic triterpenes have antiviral activity, one of which is asiatic acid. The aims of this study are to obtain the affinity and interactions of asiatic acid derivative structures in inhibiting the main protease of SARS-CoV-2. The research method was molecular docking of asiatic acid and its derivatives against the main protease of SARS-CoV-2 (6LU7) consisting …

Dermaseptin-Based Antiviral Peptides To Prevent Covid-19 Through In Silico Molecular Docking Studies Against Sars-Cov-2 Spike Protein, Taufik Muhammad Fakih

Pharmaceutical Sciences and Research

A pandemic coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now been declared a global pandemic by the World Health Organization. The search for new drugs, especially by utilizing antiviral peptides is a very potential area. Through this study, protein-peptide docking and protein-protein docking simulations were conducted using in silico methods to identify, evaluate, and explore the molecular affinity and interaction of dermaseptin peptide molecules produced by frogs of the genus Phyllomedusa against the SARS-CoV-2 spike protein macromolecule, and its effect on attachment to the surface of the ACE-2 (Angiotensin Converting Enzyme-2) receptor. …

Hybrid Cyclic/Linear Peptides In A Multi-Component Lipid Structure As A Sirna Delivery System, Abdulaziz Alasmari

Pharmaceutical Sciences (MS) Theses

Delivering siRNA is challenging due to many obstacles, such as extremely short in vivo half-life, rapid elimination via glomerular filtration, and inability to cross cell membranes due to the hydrophilic and negatively-charged nature. Thus, a delivery system is needed to deliver the siRNA into the cells by crossing the negatively-charged phospholipid cell membrane. The goal of this project was to design hybrid cyclic-linear peptides as siRNA delivery system. We designed and synthesized hybrid cyclic-linear peptides [R5K]W5, [R6K]W6, and [R5K]W7 containing positively-charged arginine residues attached to hydrophobic tryptophan chains for more efficient interaction with siRNA and to improve siRNA internalization into …

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against …

Foundational Research And Nih Funding Enabling Emergency Use Authorization Of Remdesivir For Covid-19, Ekaterina Galkina Cleary, Matthew J. Jackson, Zoë Folchman-Wagner, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Emergency Use Authorization for remdesivir months after discovery of COVID-19 is unprecedented. Typically, decades of research and public-sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to remdesivir’s biological target, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research 2000–2019. There were 6,567 RdRp-related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project …

Nih Funding For Research Underlying New Cancer Therapies, Ekaterina Galkina Cleary, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Contemporary discovery and development of cancer drugs are based on the model that investments in basic biomedical science will provide insights that can be translated into new cures. In the USA, basic research is primarily funded by the National Institutes of Health (NIH),1 which allocates half of its research budget to basic science,2 with smaller amounts contributed by philanthropy, academics, or industry.1 Basic science is formally defined as the “systematic study directed toward fuller knowledge or understanding of the fundamental aspects of phenomena and observable facts without specific application towards processes or products in mind”.3 However, science is often useinspired,4 …

A Role For Retinoids In The Treatment Of Covid-19?, Steven E. Trasino

Publications and Research

The 2020 global outbreak of the novel coronavirus (SARS-CoV-2 or COVID-19) is a serious threat to international health, and thus, there is an urgent need for discoverynof novel therapies or use of repurposed drugs that can make a significant impact on slowing the spread of the virus. Type 1 interferons (IFN-I) are a family cytokines of the early innate immune response to viruses that are being tested against SARSCoV- 2. However, coronaviruses similar to SARS-CoV-2 can suppress host IFN-I antiviral responses. Retinoids are a family molecules related to vitamin A that possess robust immune-modulating properties, including the ability to increase …

Iv Amiodarone Vs Iv Sotalol For The Use In Postoperative Junctional Ectopic Tachycardia (Jet): A Randomized Study, Tanner Isaacson

Research Days

No abstract provided.

Commentary: Phytocannabinoids As Therapeutic Agents To Combat Chronic Gingival Disease., Nick Narek Ohanian

Pacific Journal of Health

The therapeutic potential of cannabis has been harnessed for thousands of years yet the United States Food and Drug Administration (FDA) has still not approved cannabis as a safe or effective drug. The FDA has, however, approved the manufacturing of pharmaceutical drugs, which contain a “synthetic version of a substance that is present in the marijuana” and other compounds that mimic its action. A search of the US National Library of Medicine and National Institute of Health for keywords “CBD” and “Periodontitis” together yields only 2 publications. Although the current State and Federal regulations on the use of cannabis for …

Ocular, Neural, And Cellular Biodistribution Of Multifunctional Antioxidants, Damian Daszynski

Theses & Dissertations

Aging is a complex biological process which stems from a growing imbalance between the regenerative capacity of an organism and endogenous as well as exogenous damaging factors. This imbalance leads to the slow deterioration of individual cells, organs, and eventually the entire organism. The free radical theory of aging combines the evolutionary and mechanistic aspects of aging, postulating that the innate process is caused by deleterious, irreversible, and inevitable changes in biological systems caused by oxidative damage that accumulates over the lifespan. Evidence of this phenomenon is supported by the pathogenesis of age-related diseases, such as age-related macular degeneration and …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks

Honors Theses

Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I concluded …

Delivery For Hydrophobic Drugs For Treating Pancreatic Cancer, Saud Almawash

Theses & Dissertations

Purpose The aim of this study was to determine whether coadministration of hedgehog (Hh) pathway inhibitor cyclopamine (CYP) and microtubule stabilizer docetaxel (DTX) as polymer-drug conjugates, methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonategraft- dodecanol-graft-cyclopamine) (P-CYP) and methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-docetaxel) (P-DTX) could synergistically inhibit orthotopic pancreatic tumor growth in NSG mice.

Methods P-DTX and P-CYP were synthesized from mPEGb- PCC through carbodiimide coupling reaction and characterized by 1H–NMR. The micelles were prepared by film hydration and particle size was measured by dynamic light scattering (DLS). Cytotoxicity, apoptosis and cell cycle analysis of P-DTX and P-CYP were evaluated in MIA PaCa-2 cells. In vivo efficacy …

Gene Delivery To The Blood-Brain Barrier For Ischemic Stroke Therapy, Wanzhu Zhao

Electronic Theses and Dissertations

Stroke is a major cause of death in the United States. We aim to develop safe and efficient approaches for the treatment of stroke. Regenerative therapies have been identified as the major need for curing stroke [1]. We explored two different carriers (poly (ethylene glycol)_5k-poly (L-aspartate-diethylenetriamine)₄₈ (PEG-DET) / Pluronic P84 (P84) and exosomes (EXOs) / microvesicles (MVs)) to deliver brain-derived neurotrophic factor (BDNF) plasmid DNA (pDNA), a functional gene encoding a neurotrophin. In the first project, our data showed that DNA nanoparticles (NPs) with 0.03% P84 was a promising formulation to deliver Luciferase pDNA into immortalized human …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Phenylpyrazalopyrimidines As Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, And Molecular Simulations, Bhupender S. Chhikara, Sajda Ashraf, Saghar Mozaffari, Nicole St. Jeans, Dindyal Mandal, Rakesh Kumar Tiwari, Zaheer Ul-Haq, Keykavous Parang

Pharmacy Faculty Articles and Research

N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC₅₀ = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% …

The Effects Of An Adenosine A(2a) Agonist As An Adjunctive Treatment To Alleviate Sensorimotor Gating Deficits In A Rodent Model Of Schizophrenia, Hannah Rauhuff

Undergraduate Honors Theses

The adenosine system has become a promising target for the treatment of schizophrenia due to its unique relationship with dopamine D₂ receptors. Dopamine D₂ receptors display heightened sensitivity in schizophrenia, and inhibition of these receptors has been shown to alleviate some of the psychotic symptoms of the disorder. Inhibition of adenosine A(2A) receptors has been shown to decrease dopamine D₂ receptor sensitivity, making this receptor a potential target for treatment of the disorder. This effect occurs because adenosine A(2A) receptors form a mutually inhibitory heterodimeric complex with dopamine D₂ receptors. The present study looked at the …

Characterization Of Novel Cb2 Agonist Smm-295 And Its Effects In Ischemia/Reperfusion Injury, Jeffrey D. Pressly

Theses and Dissertations (ETD)

Acute kidney injury (AKI) is a major problem clinically affecting up to two-thirds of intensive care unit patients, and results in increased hospitalization time, the risk of developing chronic kidney disease, and mortality. Hallmarks of AKI include tubular cell death and a decrease in renal perfusion which leads to decreases in renal function following injury. For 20 years the pathophysiology of AKI has been well established. However, therapies for AKI have shown minimal to no success clinically. The work here describes our efforts to further categorize the effects of CB2 activation, a possible novel therapeutic target in AKI.

There is …