Medicinal Chemistry and Pharmaceutics Commons^™

Current And Potential Applications Of Simultaneous Dsc-Ftir Microspectroscopy For Pharmaceutical Analysis, Shan-Yang Lin

Journal of Food and Drug Analysis

Quality control (QC) is the most important key issue in the pharmaceutical industry to ensure the quality of drug products. Many analytical instruments and techniques in pharmaceutical analysis are applied to assess the quality and quantity of the drugs. In the current and future trends, a combination of digitization, automation and hyphenation with high throughput on-line performance will be the topics for the future of pharmaceutical QC. The hyphenated analytical techniques have recently received great attention as unique means to solve complex analytical problems in a short period of time. This review article is an update on the recent potential …

Investigations Into The Cellular Target Of 4-Trifluoromethoxy Chalcone Via Darts Method, Jordan Stacy

Undergraduate Theses

Cellular drug target discovery is an important step in any drugs journey from bench to bedside. This is true for our lab's molecule of interest, the Chalcone. The Chalcone molecule and its derivatives have been identified as small, plant-derived secondary metabolites that, when interacting with human cancer cell lines, trigger apoptotic pathways leading to varying levels of cell death. One derivative, 4-Trifluoromethoxy Chalcone (4TFM), was identified through screenings as inducing the highest death rate in A549 cancer cells, in conjunction with having the lowest IC50, making it a good candidate to use in searching for the currently unknown cellular target …

Surface-Eroding Drug Delivery Films For Sequential And/Or Intermittent Release Of Psychoactive Drugs, Jason Price

Honors Theses

ABSTRACT JASON BLAKE PRICE: Surface-Eroding Drug Delivery Films for Sequential and/or

Intermittent Release of Psychoactive Drugs For patients with psychiatric diseases, adherence to medication schedules, medication

errors, and abuse are common issues. Promising new forms of therapy for these patients, such as micro-dosed lysergic acid diethylamide (LSD), where patients receive 10-20% of a full dose every third day, present further drug delivery challenges. Sequential or intermittent release of drugs from an implanted device could ensure long-term drug compliance, automate drug dosing during the life of the implant, and eliminate potential for abuse and medication errors. To this end, we generated …

Hyperoxia-Induced Cardiac Pathophysiology In Guinea Pig Hearts, Zain Ul Abidin

USF Tampa Graduate Theses and Dissertations

Hyperoxia, is regularly introduced to critically ill patients in ICU. Nevertheless, recent studies have shown the negative effects of this treatment on patients in critical care, including increased rates of lung and cardiac injury and thereby high in-hospital mortality. Large part of the literature related to hyperoxia was majorly focused on lung injury, with no or minimal investigations on cardiac injury. Our lab is the first to investigate the effect of hyperoxia on cardiac pathophysiology in mice and showed that mice exposed to hyperoxia for 3 days demonstrated brady-arrhythmia, cardiac hypertrophy, QTc prolongation along with other electrical remodeling and functional …

Development Of Continuous Flow Sonogashira Coupling Of Lead Anti-Cancer Small Molecule Inhibitors For Potential Treatment Of Acute Myeloid Leukemia, Yuta W. Moriuchi, Shruti A. Biyani, David H. Thompson

Discovery Undergraduate Interdisciplinary Research Internship

As the technology for science develops, the research strategy in medicines and therapeutics also improves. In this paper, I will cover the process of Sonogashira cross-coupling and Amide Coupling reaction for an anticancer agent in both batch and flow chemistry. Continuous Flow Chemistry has advantages such as being more efficient, safer, and faster. This paper studies the synthesis of HSNO608, an anticancer lead compound for Acute Myeloid Leukemia (AML), which has a specific potent activity to FTL3 Kinase. Inhibition of FLT3 Kinase leads to inhibition of downstream pathways such as MPK and P13K pathways. In this two-step experiment, the Sonogashira …

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 …

Investigating The Novel Role Of Dextromethorphan In Mitigating Oxidative Stress Induced Changes In Retinal Pigment Epithelial Cells (Rpe), Zeinab A. Mohamed

USF Tampa Graduate Theses and Dissertations

Oxidative stress contributes to the degeneration of retinal pigment epithelial (RPE) cells and photoreceptors that lead to the dry form of age-related macular degeneration. Activation of N-Methyl-D-aspartate (NMDA) receptors contributes to the increase of free radicals that induce oxidative stress-induced changes. Our study investigates if Dextromethorphan, an NMDA receptor antagonist, reverses oxidative stress-induced changes in RPE. We used Paraquat and H2O2 as oxidative stress-inducing agents to induce oxidative damage in human ARPE-19 cells. To illustrate the change in cell viability and measure the apoptosis of ARPE-19 cells from oxidative damage, we performed MTT assay and Annexin V-DAPI flow cytometry analysis. …

Drug Candidates Targeting Hsp90/Cdc37 For The Treatment Of Neurodegenerative Disease, Ryan Martin

USF Tampa Graduate Theses and Dissertations

Neurodegenerative disease refers to the death of specific populations of neurons that canresult in dementia, loss of voluntary muscle motility, and other abnormalities. Two major neurodegenerative diseases are Alzheimer’s disease (AD) and Parkinson’s disease (PD), which are linked to abnormalities in Tau and a-synuclein proteins, respectively. Currently, there is no cure for these diseases. Our group and others have shown that chaperone proteins play a critical role in the processing of Tau and a-synuclein. The inhibition of the Hsp90/Cdc37 chaperone complex is shown to affect the levels of these two proteins. Hence, we hypothesized that a drug molecule, conglobatin (Cb), …

Glutathione-S-Transferase Mu 1 (Gstm1) Gene Augmentation Attenuated Oxidative Stress Induced Changes In Retinal Pigment Epithelium Cells (Rpe), Riddhi Sandeep Vichare

USF Tampa Graduate Theses and Dissertations

Purpose: Loss of Retinal Pigment Epithelial (RPE) cells and photoreceptors leads to Age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly worldwide. Oxidative stress-mediated damage is one of the factors that impair the survival of RPE and photoreceptors in dry-AMD. We sought to determine the role of human Glutathione S-Transferase Mu-1 (GSTM1) in protecting RPE cells from oxidative stress-induced changes.

Method: We cloned human GSTM1 cDNA with P2A tag into a lenti-plasmid vector and later made a lentivector to express GSTM1. After that, we infected human retinal pigment epithelial cells (ARPE-19), screened stable ARPE-19 cells …

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. …

A Convenient And Sensitive Colorimetric Iodide Assay Based On Directly Inducing Morphological Transformation Of Gold Nanostars, Rongju Zhou, Xiaohui Huang, Qingxiao An, Weizhen Xu, Yi Liu, Dong Xu, Suyan Wang, Qinlu Lin, Jianglin Zhang

Journal of Food and Drug Analysis

We propose a convenient and easy colorimetric assay for highly sensitive detection of iodide by using gold nanostars (GNSs) as probes. The assay relies on that iodide directly changes the morphology of GNSs and alters their longitudinal localized surface plasmon resonance (LSPR) without surface modifications and the use of other reagents. Upon increasing iodide concentration, GNSs gradually transformed to sphere gold nanoparticles, the absorbance at longitudinal LSPR decreased, and solution color varied from greenish blue to red, as confirmed by the UV-Vis absorption spectroscopy and transmission electron microscopy. With this strategy, as low as 0.005 μM of iodide can be …

Quercetin Blocks The Aggressive Phenotype Of Triple Negative Breast Cancer By Inhibiting Igf1/Igf1r-Mediated Emt Program, Wei-Jen Chen, Jie-Heng Tsai, Li-Sung Hsu, Chih-Li Lin, Hui-Mei Hong, Min-Hsiung Pan

Journal of Food and Drug Analysis

The cancer-preventive activities of quercetin have been extensively studied in invasive breast cancer; however, the role of quercetin on triple-negative breast cancer (TNBC) with overexpression of insulin-like growth factor-1 receptor (IGF1R) has not been resolved. In this article, we demonstrated that quercetin inhibited the activation of IGF1R and its downstream kinases Akt and Erk1/2 in a dose-dependent manner in human MDA-MB-231 breast cancer cells (TNBC cell line). Related to this, quercetin markedly suppressed the metastatic phenotype and epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells by inhibiting the expression of EMT transcription factors Snail and Slug. Quercetin also increased the secretion of …

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) …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …

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 …