Medicinal Chemistry and Pharmaceutics Commons^™

An In Silico Study Of The Delta Opioid Receptor Using Small Molecules, Emily Dean

Theses and Dissertations

The DOR is the least studied out of the three opioid receptors (Mu, Kappa, and Delta). The most is known of the Mu Opioid receptor (MOR) and the drugs that target it have led to the global opioid epidemic due to their adverse effects of tolerance and addiction. The DOR is not known for the same adverse effects and therefore, is a promising pharmacological target for the development of new opioid ligands. In this thesis, molecular modeling, simulations and other computational methods are introduced in Chapter 1 where these methods are used to study the activation mechanism of DOR (Chapter …

Supporting The Protect Initiative, Josh Lefton, Jackson Murray, Ahmed Thabet, Sriram Baireddy, Prakash Shukla, Mridul Gupta, Reagan Becker, Julie Ertle, Tony Doan, Aerin Yang

Purdue Journal of Service-Learning and International Engagement

Recently, medication dosage errors have received more political and media attention. Dosage errors are the most common medical errors, affecting about 1.5 million people annually.

Furthermore, U.S. poison-control centers reported more than 200,000 cases per year of medication errors. These cases result in medical costs of around $3.5 billion, and children under 6 years old constitute approximately 30% of these cases.

The PROTECT Initiative (Preventing Overdoses and Treatment Errors in Children Taskforce) was launched in 2008 as a collaborative effort between public health agencies and patient advocates to minimize dosage errors.

In alignment with the PROTECT Initiative effort, this project …

Effect Of Hyperoxia On Cardiac Pathophysiology In Female Guinea Pig Hearts, Chayapatou Chayawatto

USF Tampa Graduate Theses and Dissertations

Hyperoxia is widely implemented in critical care and ICU patients. The administration of a high concentration of inspired oxygen to the lung can unknowingly cause hyperoxia and thereby damaging the lungs and heart due to oxidative stress. Technically, hyperoxia occurs when the patient receives PaO2 > 200 mmHg. Major research focused on hyperoxia-induced lung injury, but nothing is known on its effect on heart. Our lab is the pioneer in understanding the effect of hyperoxia on cardiovascular remodeling using mice model. Previous results show that mice under 72 hours of hyperoxia present severe cardiac pathophysiology. This research uses Guinea pigs, which …

Association Between Use Of Remdesivir And Bradycardia, Gibret Umeukeje

USF Tampa Graduate Theses and Dissertations

Remdesivir received the first emergency use authorization from the FDA for the treatment of COVID-19. Multiple adverse drug reactions (ADR) have been reported since its approval in October 2020. Bradycardia, defined by a decrease in heart rate has been reported as an adverse event for patients receiving remdesivir for COVID-19 treatment. The purpose of the research is to systematically investigate the frequency of occurrence of bradycardia in adults receiving remdesivir using clinical data derived from the FDA Adverse Event Reporting System (FAERS) database. Patients receiving remdesivir were compared to those receiving Paxlovid, Regen-Cov, and Dexamethasone for COVID-19 treatment to see …

Screening Pathological Protein Specific Antibodies As Biomarker Discovery Tools For Neurodegenerative Disease, Yitong Li

USF Tampa Graduate Theses and Dissertations

With the increase in the average life span, the incidence of neurodegenerative diseases also increases, among which Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common types of neurological disorders. AD and PD share the same pathogenic mechanism that involves a class of proteins called beta-amyloid (Aβ), which, under the induction of some factors, changes from its natural monomeric state to the oligomers containing β-sheet, which is neurotoxic and thus leads to cell damage or apoptosis. This study focused on the selection of antibodies used as biomarkers for AD and PD. The selection of antibodies was based …

Seasonal Affective Disorder Treatment: Light Therapy Versus Ssri Therapy, Gabriella M. Hinde, Hannah Dyer, Ash Werner, Michaela Cisowski

Non-Thesis Student Work

To determine the effect of pharmacological and nonpharmacological treatments for seasonal depression in college students, we asked the following evidence-based PICO question: In college students (ages 18-25) with seasonal affective disorder (SAD), how does SSRI (Selective Serotonin Reuptake Inhibitor) therapy compared to light therapy affect seasonal depression syndrome? Seasonal affective disorder is synonymously used with the terminology seasonal depression due to the clinical manifestations that encompass depression, such as low energy, feelings of sadness, emptiness, or hopelessness. SAD begins in the fall months and peaks in the winter months due to a decrease in Vitamin D and ultraviolet (UV) ray …

Wastewater-Informed Public Health Intervention Playbook

Sustain Magazine

As the SARS-CoV-2 pandemic quickly spread from country to country and continent to continent in 2020, governments and scientists needed a way to track COVID-19 through populations in order to position public health interventions in the most impactful locations. Having a decision-based risk framework may help to guide policy creation that could minimize or prevent possible outbreaks and surges of infection within communities. The University of Louisville in partnership with Louisville’s Department of Public Health and Wellness tested this strategy in 2021 and 2022. This Wastewater-Informed Public Health Intervention Playbook describes the decisions and actions of that academic and public …

In Silico Screening Of Violacein As An Epidermal Growth Factor Receptor Inhibitor, Smitha S Bhat, Sindhu R, Shashanka K Prasad

International Journal of Health and Allied Sciences

EGFR is a key player in the signalling cascades of various kinds of cancers and tyrosine kinase inhibitors block EGFR signalling. Natural products have long been used as candidates for therapy in the management of cancer. Violacein, a bacterial pigment, has been known for its numerous biological applications such as antimicrobial, antileishmanial, antiviral, as well as antitumoral. Computational studies have concluded that it may have activity against cancers like pancreatic cancer, thyroid cancer, colorectal cancer, and endometrial cancer indicating its potential application as a broad range of anti-cancerous drug. This study aimed to perform the molecular docking of violacein with …

Diallyl Disulfide Inhibits Proliferation, Epithelial—Mesenchymal Transition, And Invasion Through Rorα-Mediated Downregulation Of Wnt1/Β-Catenin Pathway In Gastric Cancer Cells, Jian Su, Hui He, Yu-Kun Li, Hong Xia, Fang Liu, Ying Zeng, Xi Zeng, Hui Ling, Bo Su, Qi Su

Journal of Food and Drug Analysis

Overactivation of Wnt/β-catenin pathway due to dysfunction of retinoid-related orphan receptor α (RORα) is related to cancer development and progression. Diallyl disulfide (DADS), an active component of garlic, has been reported in our previous study for upregulation of RORα expression in gastric cancer (GC) cells. It remains to be elucidated the role and mechanism of RORα in DADS against GC. This study revealed that DADS treatment resulted in reduced expression levels of Wnt1, β-catenin, TCF-4, intranuclear β-catenin and p-β-catenin in GC cells, concomitant with the compromised expression of β-catenin target genes (Axin, c-Jun, and c-Myc). RORα overexpression augmented DADS-induced downregulation …

Melatonin Exerts Anti-Fibrinolytic Effects By Regulating Il-1Β-Induced Changes In Upa, Upar, And Pai-1 Expression/Production In Human Dental Pulp Cells, Mei-Chi Chang, Bor-Hao Zhong, Hui-Na Lee, Fu-Hsiung Chuang, Ming-Shu Lee, Hsiao-Hua Chang, Yu-Hwa Pan, Jiiang-Huei Jeng

Journal of Food and Drug Analysis

Interleukin-1b (IL-1β) is a pro-inflammatory cytokine and its expression is increased in inflamed dental pulp. IL-1β affects plasminogen activation system molecules, which are crucial for tissue inflammation, fibrinolysis, matrix turnover, and cell adhesion and migration. Melatonin, which provides circadian and seasonal signals, is a physiological endocrine generated by the pineal gland. It has anti-oxidant and anti-inflammatory properties. Studies are warranted to determine whether melatonin prevents IL-1β-induced expression/production of plasminogen system molecules. Human dental pulp cells (HDPCs) were exposed to IL-1β or melatonin alone or to IL-1β with/without pretreatment with melatonin or other inhibitors. The mRNA expression of uPA, uPAR, and …

Stress Amelioration And Anti-Inflammatory Potential Of Shiikuwasha (Citrus Depressa Hayata) Essential Oil, Limonene, And Γ-Terpinene, Yonathan Asikin, Kuniyoshi Shimizu, Hironori Iwasaki, Hirosuke Oku, Koji Wada

Journal of Food and Drug Analysis

Shiikuwasha (Citrus depressa Hayata) essential oil (SEO) extracted from Shiikuwasha fruit pulp contains two major volatile components, limonene and γ-terpinene (56.56–57.31 and 24.41–24.98%, respectively). In this study, we showed that the aroma streams of SEO, limonene, and γ-terpinene exhibited significant physiological stress amelioration effects in nine healthy female panelists tested in a 30-min visual display task. While SEO administration significantly reduced work errors by 15 min compared to the odorless control condition, the limonene stream reduced work errors only at the first and fourth 5-min intervals, and the γ-terpinene effect lasted only for the initial 5-min. However, γ-terpinene inhalation …

Composition Decipherment Of Ficus Pumila Var. Awkeotsang And Its Potential On Covid-19 Symptom Amelioration And In Silico Prediction Of Sars-Cov-2 Interference., Hao-Chun Hu, Szu-Yin Yu, Xiao-Shan Hung, Chun-Han Su, Yu-Liang Yang, Chien-Kei Wei, Yuan-Bin Cheng, Yang-Chang Wu, Chia-Hung Yen, Tsong-Long Hwang, Shu-Li Chen, István Szatmári, Attila Hunyadi, Yi-Hong Tsai, Fang-Rong Chang

Journal of Food and Drug Analysis

The jelly from achenes of Ficus pumila var. awkeotsang (FPAA) is a famous beverage ingredient in Taiwan. In this work, ficumarin (1), a new compound was obtained from its twigs (FPAT) and elucidated with comprehensive spectroscopic data. The biosynthetic origin was proposed from the p‐coumaroyl‐CoA pathway. Alloxanthoxyletin, betulinic acid, and catechin were identified as the major and active constituents responsible for relieving neutrophilic inflammation by FPAT. Among them, the most potent alloxanthoxyletin was found to interact with PRO350 and GLU377 of human INOSOX. Further, Nrf2 activating capacity of the FPAT fraction and its coumarins was confirmed. With …

Phytochemical Characterization, Antioxidant Potential, And Health Risk Assessment Of Radix Oryzae Glutinosae, Hai-Ping Liu, Jian-Feng Tang, Kai Ren, Tong-Jun Chen, Ping-Ping Zhu, Dong-Dong Sun, Wei-Yun Wang

Journal of Food and Drug Analysis

Radix Oryzae Glutinosae (ROG) has been used as a traditional anhidrotic agent in China. Ten samples were systematically assessed based on four aspects of their chemical profiles and antioxidant activity. The former was achieved using ultraviolet-visible spectra (UV), infrared absorption spectra (IR), proton nuclear magnetic resonance spectroscopy (¹H NMR), and inductively coupled plasma-mass spectrometry (ICP-MS) fingerprints, and antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, the 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assay, and the ferric reducing antioxidant power (FRAP) assay. The presence of amino acids, flavonoids, organic acids, and sugars was indicated in all samples. A hierarchical …

Exploring The Relationship Between Metabolite Composition And The Cold/Hot Properties Ascribed In Traditional Chinese Medicine By Mass Spectral Molecular Networking–A Pilot Study, Chun-Han Su, Yu-Chieh Cheng, Kuei-Hung Lai, Yu-Chia Chang, Chi-Hui Sun, Po-Wen Tu, Ching-Chih Lin, Tsong-Long Hwang, Yu-Liang Yang

Journal of Food and Drug Analysis

Traditional Chinese medicine (TCM) has been applied to improve human health for millennia. In the TCM system, “medicinal property” (yao xing; hot and cold properties) is a core concept used to describe the influences of medicinal materials on human physiological conditions, and metabolites are believed to be one of the major ingredients of TCMs that affect their medicinal property. However, due to a lack of comprehensive analyses of TCM metabolomes, information about the relationships between TCM metabolite composition and medicinal property remains limited. In this pilot study, a mass spectral molecular networking-based platform was established and applied to …

Quantification Of Anthocyanosides In Grapes By Quechers And Biphenyl-Uhplc Tandem Mass Spectrometry, Lun-Chi Yang, Sung-Fang Chen

Journal of Food and Drug Analysis

In this study, the QuEChERS and UHPLC-MS/MS method using a biphenyl stationary phase was developed and applied for the rapid separation of 12 anthocyanosides in grapes. Efficient separation was achieved for a wide range of mono- and un-glycosylated anthocyanosides. The linear ranges of the target anthocyanosides were 0.5 to 500 ng mL⁻¹. The intra- and inter-day precisions were both below 11.8%. Anthocyanosides in grapes from different sources were successfully quantified. Thus, the developed QuEChERS and UHPLC-MS/MS method provide an attractive alternative for the quantification of anthocyanosides in grapes.

Fluorescence Detection Of Malachite Green In Fish Based On Aptamer And Sybr Green I, Jia Wang, Chengyi Hong, Zhengzhong Lin, Zhi-Yong Huang

Journal of Food and Drug Analysis

A simple fluorescence method to quantitatively monitor malachite green (MG) was introduced based on the conformation switch effect of MG-aptamer (Apt) and the fluorochrome of SYBR Green I (SGI). SGI can embed in the stem–loop structure of Apt to produce fluorescence. However, the fluorescence will be quenched when MG is introduced because of the specific binding of Apt to MG. Under the optimal conditions, the fluorescence method displayed excellent linear relationship between the fluorescence quenching efficiencies and the MG concentrations ranging from 0.02 μmol L⁻¹ to 1.0 μmol L⁻¹. The detection limit of the method was 0.67 …

Bromelain Activates The Amp-Activated Protein Kinase-Autophagy Pathway To Alleviate Hepatic Lipid Accumulation, Po-An Hu, Man-Chen Hsu, Szu-Han Chen, Chia-Hui Chen, Yu Ru Kou, Jenq-Wen Huang, Tzong-Shyuan Lee

Journal of Food and Drug Analysis

Bromelain, a cysteine protease found in pineapple, is known to exert protective effects against non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. In this study, we aimed to investigate the molecular mechanisms underlying the beneficial effects of bromelain using in vivo and in vitro models. C57BL/6 mice were fed a high-fat diet (HFD) with or without bromelain (20 mg/kg/day) for 12 weeks. We found that treatment with bromelain alleviated hepatic lipid accumulation accompanied by the activation of AMP-activated protein kinase (AMPK) and autophagy flux, as evidenced by the elevated levels of phosphorylated AMPK, ATG5, ATG7, LC3-II, and …

Metabolism-Involved Drug Interactions With Traditional Chinese Medicines In Cardiovascular Diseases, Ren-Jong Liang, Shu-Hao Hsu, Tien-Yu Chang, Tzu-Yi Chiang, Hong-Jaan Wang, Yune-Fang Ueng

Journal of Food and Drug Analysis

Herbal medicines have been widely used for the past millennia. Traditional Chinese medicine (TCM) is a major modality in Chinese medical care and has garnered global attention owing to its pharmacological effects and multi-targeted actions. The increased incidence of sequential or concurrent use of herbs and drugs in patients forces us to consider herb-drug interactions (HDIs) in this modern era. One of the main causes of HDIs is modulation of drug metabolism, in which cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT), and transporters play primary roles. In this review, we focus on in vivo studies of HDIs, particularly in the treatment of …

Real-World Evidence Of The Herb-Drug Interactions, Hsueh-Yi Pan, Li-Wei Wu, Pin-Chun Wang, Ping-Hung Chiu, Meng-Ting Wang

Journal of Food and Drug Analysis

Herbal medicine (HM) is a type of medicine that uses active ingredients made from plants to treat diseases and maintain health and wellbeing. Due to its increasing worldwide usage, the possibility of HMs and conventional drugs being concurrently used is high, potentially leading to adverse events resulting from herb-drug interactions. Despite the safety concerns regarding such interactions, few studies have been conducted for assessing clinical consequences of using HMs with conventional drugs in real-world settings. As clinical trials are not forthcoming rapidly enough to provide the evidence for herb-drug interactions, observational studies are considered as an alternative approach. The present …

Preclinical Development Of Novel Chemotherapeutic Agent Ac1lpszg: Formulation Optimization, In Vitro Characterization, And In Vivo Pharmacokinetics, Ritu Gupta

Dissertations (2016-Present)

Preclinical development of novel chemotherapeutic agent AC1LPSZG, a mammalian target of rapamycin (mTOR) inhibitor, involved development of sensitive reverse-phase ultra-performance liquid chromatography (UPLC) and LC-MS/MS methods for quantification of AC1LPSZG in in vitro study samples and rat plasma, respectively. Pharmacokinetic studies were done in SD rats after intravenous injection of cosolvent formulations. The resulting pharmacokinetic parameters were analyzed using non-compartmental analysis (NCA) and two-compartmental modeling. Poly (D, L-lactic-co-glycolic acid) (PLGA) is most used biodegradable synthetic polymer for nano drug delivery due to its non-toxic and biodegradable nature, and tunable release properties. PLGA nanoparticles (NPs) were prepared by ‘nanoprecipitation’ technique using …