Medicinal Chemistry and Pharmaceutics Commons^™

Synthesis Of 1-(4-Ethoxy-3-Methoxybenzyl)-1,10-Phenanthrolin-1-Ium Bromide And Its Evaluation As Antiplasmodium Through Heme Polymerization Inhibitory Activity (Hpia) Assay, Dhina Fitriastuti, Viny Alfiyah, Mustofa Mustofa, Jumina Jumina, Muhammad Idham Darussalam Mardjan

Makara Journal of Science

This study describes the development of N-benzyl-1,10-phenantrolinium salt as an antiplasmodium agent. The salt, that is, 1-(4-ethoxy-3-methoxybenzyl)-1,10-phenanthrolin-1-ium bromide, was prepared using vanillin as the starting material in four simple synthetic steps. First, the alkylation of vanillin using diethyl sulfate produced 4-ethoxy-3-methoxybenzaldehyde in 79% yield. Second, the reduction of the protected vanillin by NaBH₄ through the grinding method allowed us to obtain 4-ethoxy-3-methoxybenzyl alcohol in 96% yield. Next, the bromination of the benzyl alcohol under solvent-free condition led to the formation of the corresponding benzyl bromide, which in turn underwent bimolecular nucleophilic substitution with 1,10-phenanthroline to produce the desired …

Use Of A Zebrafish Model To Identify Anticonvulsant Properties Of Cannabinoid And Terpenoid Extracts And Mixtures, Courtney Murr

LSU Master's Theses

Epilepsy is a complex group of neurological disorders affecting approximately 65 million people worldwide. Animal models reveal the activation of cannabinoid receptor 1 and cannabinoid receptor 2 reduces the severity of seizures associated with epilepsy. Trials of phytocannabinoids in mammals demonstrate their efficacy of reducing the severity of epileptic seizures. Numerous terpenoid compounds are present in Cannabis plants but most have yet to be clinically investigated. The goal of this research was to use zebrafish (Danio rerio) to identify the potential anticonvulsive properties of phytocannabinoid and terpenoid compounds. During acute cannabinoid exposures, 7-days-post-fertilization (7 dpf) zebrafish larvae were …

New Psychoactive Substances In Taiwan: The Current Situation And Initiative For Rational Scheduling, Wen-Jing Yu, Linda B. Cottler, Jih-Heng Li

Journal of Food and Drug Analysis

Use of New Psychoactive Substances (NPS) has posed a global threat to public health and the security of the population. As of December 2019, the NPS items identified in total have outnumbered by three to one the controlled substances listed in the 1961 and 1971 UN Drug Conventions. However, most of these NPS have not been scheduled by the United Nations because of their easy modification on the chemical structures to shun control. Currently, the scheduling and control of NPS is mostly at the national level and a rational scheduling of NPS by objective assessments is essential but often lacking. …

The Bioactivities Of Resveratrol And Its Naturally Occurring Derivatives On Skin, Ming-Hsien Lin, Chi-Feng Hung, Hsin-Ching Sung, Shih-Chun Yang, Huang-Ping Yu, Jia-You Fang

Journal of Food and Drug Analysis

Resveratrol has been extensively reported as a potential compound to treat some skin disorders, including skin cancer, photoaging, allergy, dermatitis, melanogenesis, and microbial infection. There has been an increasing interest in the discovery of cosmetic application using resveratrol as the active ingredient because of its anti-aging and skin lightening activities. The naturally occurring derivatives of resveratrol also exert a beneficial effect on the skin. There are four groups of resveratrol derivatives, including hydroxylated compounds, methoxylated compounds, glycosides, and oligomers. The major mechanism of resveratrol and its derivatives for attenuating cutaneous neoplasia, photoaging and inflammation, are related with its antioxidative activity …

Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, Ethige Isuru P. Silva, Pathmakumara Jayasingha, Saman Senanayake, Anura Dandeniya, Dona Helani Munasinghe

International Journal of Speleology

The emergence of antibiotic resistance is a global health crisis, thus the search for novel antimicrobial compounds has become a continuous necessity. Underexplored and extreme environments, such as cave ecosystems, have been identified as a promising potential source for the discovery of novel microorganisms with novel antimicrobial compounds (AMC). This study presents the first cave microbiological investigation in Sri Lanka, with a special preference for bioprospecting of novel AMC. The cave sediment characterization demonstrated the presence of close to strong acidic conditions (pH 3.1 – 3.3) and thus indicates the possibility of isolating acidophilic microorganisms. Eight cave wall/ceiling fungal strains …

Structural Characterization And In Vitro Antiproliferative Activity Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa

Pharmaceutical Sciences (PhD) Dissertations

Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling, in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and in vitro antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds.

Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma

Theses and Dissertations

Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Achieving Better Care In Pennsylvania By Allowing Pharmacists To Practice Pharmacy, Travis Murray

Dickinson Law Review (2017-Present)

Traditionally, state legislatures implemented Prescription Drug Monitoring Programs (“PDMPs”) to assist prescribers, pharmacists, and law enforcement in identifying patients likely to misuse, abuse, or divert controlled substances. PDMP databases contain a catalog of a patient’s recent controlled substances that pharmacies have filled, including the date, location, the quantity of medication filled, and the prescribing health care provider. Prescribers in Pennsylvania have a duty to query the PDMP before prescribing controlled substances in most clinical settings. Pharmacists have a similar duty in Pennsylvania to dispense safe and effective medication therapy to patients and to screen patients for potential signs of misuse, …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Lemongrass (Cymbopogon Citratus) Ethanolic Extract Exhibited Activities That Inhibit -Glucosidase Enzymes And Postprandial Blood Glucose Elevation, Maria Dewi Puspitasari Tirtaningtyas Gunawan Puteri, Felicia Melissa Tjiptadi, Phebe Hendra, Filiana Santoso, Zalinar Udin, Nina Artanti, Florence Ignatia Florence Ignatia

Makara Journal of Science

Lemongrass is a common ingredient in Indonesian traditional herbal medicine that potently inhibits carbohydrate hydrolysis. In this study, the in vitro α-glucosidase inhibitory (AGI) activity of lemongrass was compared with its in vivo activity to retard postprandial blood glucose elevation, and the bioactive compounds responsible for these activities were observed. Both water and ethanolic extracts of lemongrass (WLG and ELG, respectively) were tested in vitro for its inhibition of the sucrose and maltose hydrolyzing activities of rat intestinal glucosidase. ELG was observed to exert higher inhibitory activities (Sucrase IC₅₀ = 8.74 mg/mL; Maltase IC₅₀ = 18.93 mg/mL) than …

Long-Acting Nanoformulated Antivirals For The Treatment And Prevention Of Hiv-1 And Hbv Infections, Dhruvkumar M. Soni Dr.

Theses & Dissertations

While antiretroviral therapy (ART) has revolutionized treatment and prevention of human immunodeficiency virus type one (HIV-1) infection, regimen adherence, viral mutations, drug toxicities, stigma and pill fatigue are limitations. These have led to the development of long acting (LA) ART. These include, but are not limited to, implantable devices, new chemical entities, prodrug modifications and nanoformulations. To these ends, this thesis focues on the transformation of nucleoside reverse transcriptase inhibitors (NRTIs) into LA parenterals, While elusive, data from our laboratories demonstrated that modifications to the PROdrug and nucleoTide technology (ProTide) enables improvements in drug apparent half-life and tissue and cell …

Hyaluronic Acid Coated Targeted Lipid Micellar Nanoparticle As A Delivery Vehicle For Lapatinib And Ketoconazole In Egfr Mutated Lung Cancer, Nadia Tasnim Ahmed

USF Tampa Graduate Theses and Dissertations

Background: According to the American Cancer Society, lung cancer was accountable for over 142,000 deaths in the USA in 2019. Common mutations related to lung cancer mainly occur in TP53, EGFR, and KRAS genes. Lapatinib is a small molecule tyrosine kinase inhibitor which acts reversibly on both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Overexpression of EGFR leads to increased production and signaling of proteins that cause upregulation of cellular proliferation, cholesterol synthesis and resistance to apoptosis. Ketoconazole is an imidazole antifungal agent which works principally by inhibiting the enzyme cytochrome P450 14α-demethylase (CYP51A1) …

Study Of Pharmaceutical Tablets Using Raman Mapping, Kyle Joseph Pauly

Honors Theses

Covalent bonds are the strongest type of bonds holding molecules together. Based on the pattern of bonding of the molecule, the atoms associated with the bond will vibrate at a specific frequency. Utilizing vibrational spectroscopy, such as Raman spectroscopy, these unique vibrational frequencies can be used to detect the presence of analytes over a selected area. Furthermore, the intensities of the vibrational modes can be tracked to comparatively quantify the concentration of analytes at various locations. This is a method of great importance due to its ability to compare pharmaceutical tablets synthesized with different techniques. Here, the presence and concentration …

Design And Synthesis Of Novel Analogs As Potential Antitubercular Agents, Peggy Mccluggage

Honors Theses

Tuberculosis (TB) is an infectious, airborne disease which primarily infects the lungs. One-third of the world’s population is currently estimated to be infected with Mycobacterium tuberculosis (Mtb), the causative agent for TB [1]. Current treatment for this disease requires at least six months of taking multiple antibiotics with undesirable side effects [2]. Difficulty in complying to this regimen as well as the prevalence of HIV/AIDS has led to antimicrobial resistance seen in Mtb. In order to combat the Multi-Drug Resistant and Extensively-Drug Resistant strains of the disease-causing bacteria, preventative care and novel antibiotics are urgently needed [3]. The purpose for …

Antidepressants Versus Music Therapy: Which Treatment Is Better For Treating Depression In Parkinson's Disease?, Emaan Dawood

Virginias Collegiate Honors Council Conference

Music and medicine are merging to treat depression in Parkinson’s disease (PD). Antidepressants, the current standard, demonstrate mixed effects in clinical trials, warranting other treatment options. Here, I compare music therapy to antidepressants in the treatment of depression in PD via literature review. Studies of depressed PD patients undergoing music therapy and/or antidepressants were reviewed with attention to variables including depression (on a patient-reported outcome) that were measured pre- and post- therapy. In the music studies, improvements were seen in depression. Methodological inconsistencies across these studies, a paucity of studies, and small sample sizes, however, necessitate more research to reach …

The Diffusion Of Artificial Intelligence/Machine Learning Methods And Data Analytics Into An Undergraduate Nursing Research Course, Mary Anne Schultz

Q2S Enhancing Pedagogy

The project is the adoption of principles of Artificial Intelligence (AI)/Machine Learning and Data Analytics into a traditional nursing research (hypothesis testing) course. Necessitated by the recent entrance of “Big Data” use in health care, there is an urgent need to inject an understanding of the AI/ML techniques necessary to extract, organize and derive meaning from this huge amount of evidence in clinical decision-making. In fact, our department recently approved the adoption of Precision Health (PH) (the clinical use of the plethora of highly-individualized data in health & medical decisions) principles into six undergraduate courses, NURS 4222 (Nursing Research & …

Parp1-Targeted Radiotherapies, Stephen Jannetti

Dissertations, Theses, and Capstone Projects

Poly-ADP-ribosylation reactions were first reported by Chambon in 1963 as enzymatic activity that increases incorporation of ATP in the presence of nicotinamide mononucleotide. In the decades since that publication, Poly(ADP-ribose)polymerase 1 (PARP1) and the PARP family enzymes have been widely studied. PARP enzymes are currently known to play various roles in mammals, including anti-aging processes, interactions with Breast Cancer Suppressor Protein-1 (BRCA1), and DNA damage repair. A significant focus of PARP1 research has been elucidating its role in DNA damage repair. PARP1 is recruited to repair single strand DNA (ssDNA) breaks, which can become double stranded DNA (dsDNA) breaks if …

Neurodevelopment Outcome Of Neonates Treated With Intraventricular Colistin For Ventriculitis Caused By Multiple Drug-Resistant Pathogens-A Case Series, Kashif Hussain, Muhammad Sohail Salat, Gul Ambreen, Javaid Iqbal

Department of Biological & Biomedical Sciences

Background: Multiple-drug-resistant Gram-negative bacteria (MDR-GNB)-associated neonatal ventriculitis is a life-threatening complication that needs timely diagnosis and effective treatment with broad-spectrum antimicrobials in critical-care settings. Inadequate penetration of antibiotics through the blood-brain barrier also demands an intraventricular (IVT) route of administration. This study reports mortality and neurodevelopmental sequelae of neonates till 18 months of age, who received IVT-colistin for treating MDR-GNB associated ventriculitis.
Methods: In a case series of seven neonates with ventriculitis due to MDR-GNB at NICU of Aga Khan University Hospital, Pakistan, between June 2015 and 2018, we reviewed IVT-colistin therapy in critically ill neonates. Treatment outcomes were assessed …

Phytochemical Screening, In Vitro Antimalarial Activity And Genetic Diversity Of Selected Asteraceae Medicinal Plants Indigenous To Thailand, Desy Liana

Chulalongkorn University Theses and Dissertations (Chula ETD)

The emergence of artemisinin resistance leaded the effort to find the new antimalarial drug or artemisinin activity booster. Due to the chance that secondary metabolites can be evolutionary conserved, combining phylogeny with ethnobotanical data for screening antimalarial activity may be helpful to predict bioactivity and minimize the expenditure and time for laboratory research. The aimed of this study is screening the antimalarial activity, phytochemicals and genetic diversity of selected Asteraceae medicinal plants generated by combinatorial phylogeny and ethnobotanical data. 733 medicinal plants were obtained from literature search however only 340 taxa were met the inclusion and exclusion criteria hence these …

Model-Based In-Vitro Pk/Pd Profiling Of Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) As Potential Sickle Cell Disease (Scd) Therapeutics, Xiaomeng Xu

Theses and Dissertations

Introduction: Allosteric effectors of hemoglobin (AEH) represent a class of synthetic aromatic aldehydes that transiently form covalent interactions (Schiff-base) with hemoglobin (Hb) to form Hb-AEH adduct, preventing the HbS polymerization and sickling of red blood cells (RBC). The overall objective of this research was to aid in the optimization of novel AEH by understanding their target-site disposition of AEH in relevant biological matrices, e.g., HbA solution, whole blood (WB) and human liver cytosol (HLC), a surrogate of aldehyde dehydrogenase (ALDH)-mediated oxidative metabolism.

Methods: A “universal” HPLC-UV/Vis assay method was developed for the quantitation of HbA-AEH adduct for chemically …

Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng

Theses & Dissertations

Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …

Computational Studies And Design Of Pparγ And Glut1 Inhibitors, Suliman Almahmoud

Theses & Dissertations

The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor of the nuclear receptor superfamily that controls the expression of a variety of genes involved in fatty acid metabolism, adipogenesis, and insulin sensitivity. PPARγ is a target for insulin-sensitizing drugs, and it plays a significant function in prostate cancer. PPARγ antagonists have anti-proliferative effects in a broad range of hematopoietic and epithelial cell lines. The ligand binding domain (LBD) of PPARγ is large and has orthosteric and allosteric binding sites. Several PPARγ-ligand co-crystal structures show two bound molecules, one to the orthosteric pocket and a second to the allosteric …

Sustainable Solutions, Fall/Winter 2020, Issue 41

Sustain Magazine

No abstract provided.

Environmentally Responsible Land Use, Spring/Summer 2010, Issue 22

Sustain Magazine

No abstract provided.

Sustainable Communities, Fall/Winter 2010, Issue 21

Sustain Magazine

No abstract provided.

Sustainable Building, Spring/Summer 2009, Issue 20

Sustain Magazine

No abstract provided.