Medicinal Chemistry and Pharmaceutics Commons^™

Sunitinib-Loaded Mpeg-Pcl Micelles For The Treatment Of Age-Related Macular Degeneration, Jarriaun D. Streets

USF Tampa Graduate Theses and Dissertations

Age-related Macular Degeneration, or AMD will be responsible for the vision impairment of more than 5 million late-aged adults in the next 30 years. Current treatment options include frequent intravitreal injections which report high levels of pain resulting in a low patient compliance. However, there are methods of drug delivery that can decrease the amount of intravitreal injections by sustaining drug release. Polymeric micelles, specifically MPEG-PCL have reported superb biocompatibility and more efficient ways of delivering anti-VEGF drugs such as Sunitinib to the posterior segment of the eye. In this study, the novel micellar formulation exhibited an average DLS particle …

Synthesis Of A Targeted Ph Responsive Nanoparticle For Controlled Release Of Actinomycin D, Alejandro Jesus Gonzalez

USF Tampa Graduate Theses and Dissertations

Out of all cancer diagnosis’s, lung cancer has the highest mortality in both sexes making it the leading cause of cancer deaths. Current therapeutic and clinical methods fail to successfully treat the disease, contributed to the development of multi-drug resistance (MDR). Hence, new therapies are needed that can exploit the tumor microenvironment (TME) to target Cancer Stem Cells (CSC). CSCs constitute a key population of the TME, promoting hypoxia, low intracellular pH, and angiogenesis. Actinomycin D (ACD) is a potent CSC inhibitor, but due to its high toxicity and lack of specificity towards cancer cells presents a need for a …

Synthesis Of Fluoroflavonoids As Potential Antioxidant Against Alzheimer’S Disease., Maali Alshammari

Graduate Student Council Research Grants

Overview: Maali Alshammari joined the lab of Professor David A. Colby in spring of 2017; she's currently a third-year Ph.D. student in medicinal chemistry in the graduate program in the Department of BioMolecular Sciences at the University of Mississippi. Maali's project involves the syntheses of fluoroflavones to improve the potency of the antioxidant activity of the original non-fluorinated flavones. The fluoroflavones will potentially be used as neuroprotective agents to prevent the toxic effect of ROS and used to prevent neurogenerative diseases like Alzheimer's.

Intellectual Merit: We are in need of medications that prevent Alzheimer's disease or even reverse its damage; …

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 & …

Catalytic, Selective, And Stereocontrolled Construction Of C4 Quaternary And Homobenzylic Dihydroisoquinolones By Sp3 C–H Benzylation, Timothy K. Beng, Antonio Moreno

All Faculty Scholarship for the College of the Sciences

C1 benzylated isoquinoline derivatives constitute the core of benzylisoquinoline alkaloids (BIAs). However, their C4 congeners remain elusive. Here, we describe a diastereoselective, catalytic, and modular C(sp³)–C(sp³) coupling protocol wherein β-amino sp³ C–H bonds of readily affordable vicinally functionalized dihydroisoquinolones are replaced by sp³ C–benzyl bonds. The method provides expedient access to C4 quaternary and homobenzylic dihydroisoquinolones, which are attractive fragments for potential drug discovery.

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 …

Atomic Force Microscopy (Afm) As A Surface Mapping Tool In Microorganisms Resistant Toward Antimicrobials: A Mini-Review, Zuzanna Grzeszczuk, Antoinette Rosillo, Oisin Owens, Sourav Bhattacharjee

Other resources

The worldwide emergence of antimicrobial resistance (AMR) in pathogenic microorganisms, including bacteria and viruses due to a plethora of reasons, such as genetic mutation and indiscriminate use of antimicrobials, is a major challenge faced by the healthcare sector today. One of the issues at hand is to effectively screen and isolate resistant strains from sensitive ones. Utilizing the distinct nanomechanical properties (e.g., elasticity, intracellular turgor pressure, and Young’s modulus) of microbes can be an intriguing way to achieve this; while atomic force microscopy (AFM), with or without modification of the tips, presents an effective way to investigate such biophysical properties …

Total Cellular Atp Production Changes With Primary Substrate In Mcf7 Breast Cancer Cells., Maggie Louie, Justin Ton, Maurice L. Brady, Diem T. Le, Jordon N. Mar, Chad A Lerner, Akos A Gerencser, Shona A. Mookerjee

Natural Sciences and Mathematics | Faculty Scholarship

Cancer growth is predicted to require substantial rates of substrate catabolism and ATP turnover to drive unrestricted biosynthesis and cell growth. While substrate limitation can dramatically alter cell behavior, the effects of substrate limitation on total cellular ATP production rate is poorly understood. Here, we show that MCF7 breast cancer cells, given different combinations of the common cell culture substrates glucose, glutamine, and pyruvate, display ATP production rates 1.6-fold higher than when cells are limited to each individual substrate. This increase occurred mainly through faster oxidative ATP production, with little to no increase in glycolytic ATP production. In comparison, non-transformed …

Serotonin 5-Ht2a And 5-Ht2c Receptors Regulate Rat Maternal Behavior Through Distinct Behavioral And Neural Mechanisms, Jun Gao, Lina Nie, Yu Li, Ming Li

Department of Psychology: Faculty Publications

Serotonin 5-HT_2A and 5-HT_2C receptors play important yet distinctive roles in the regulation of rat maternal behavior. The present study investigated their neural substrates and explored the possible behavioral mechanisms (i.e., behavioral organization or maternal motivation). Sprague-Dawley postpartum females were microinjected with either a selective 5-HT_2A agonist (TCB-2, 0.4 or 4.0 μg/side) or a 5-HT_2C agonist (MK212, 2.5 or 5.0 μg/side) into the medial prefrontal cortex (mPFC) or ventral tegmental area (VTA). Ten and 60 min later, their maternal activities were observed in the home cage; and their motivational responses towards pups were examined in a …

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 …

Pharmacology Of Fentanyl-Related Substances In Mice Reveals Potential Therapeutics With Improved Protective Indices, Neil B. Varshneya

Theses and Dissertations

Fentanyl-related substances constitute a class of compounds that were originally developed in the latter half of the 20th century as combination analgesic-anesthetic agents. Today, many of these compounds have emerged in the recreational drug marketplace as adulterants to heroin, counterfeit prescription pills, and even as standalone products designed to circumvent drug control laws. The objective of this dissertation was to identify the structural determinants of fentanyl analogs that could affect the potency and efficacy for eliciting their therapeutic and toxic effects to identify candidates of potential therapeutic interest. To accomplish this objective, thirty-eight fentanyl-related substances, in addition to the MOR …

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 …