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Α-Glucosidase Inhibitors From Dendrobium Delacourii, Dendrobium Gibsonii And Aerides Multiflora, May Thazin Thant

Chulalongkorn University Theses and Dissertations (Chula ETD)

In this study, three plants from the Orchidaceae family, i.e., Dendrobium delacourii, Dendrobium gibsonii, and Aerides multiflora, were investigated for their chemical constituents and α-glucosidase inhibitory activities. A total of thirty compounds were isolated and structurally characterized. Eleven known compounds were identified from Dendrobium delacourii, including hircinol, ephemeranthoquinone, densiflorol B, moscatin, 4,9-dimethoxy-2,5-phenanthrenediol, gigantol, batatasin III, lusianthridin, 4,4',7,7'-tetrahydroxy-2,2'-dimethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene, phoyunnanin E, and phoyunnanin C. Two new compounds, i.e., dihydrodengibsinin and dendrogibsol, were isolated from Dendrobium gibsonii, along with seven known compounds including ephemeranthol A, dengibsinin, nobilone, aloifol I, lusianthridin, denchrysan A, and 4-methoxy-9H-fluorene-2,5,9-triol. Four new compounds, i.e., aerimultins A-C and dihydrosinapyl dihydroferulate, …

Lipase Inhibitors From Dendrobium Senile, Myat Pann Phyu

Chulalongkorn University Theses and Dissertations (Chula ETD)

Obesity is characterized as an abnormal lipid metabolism due the imbalance between the energy intake and output. Pancreatic lipase is secreted by the pancreas and plays an important role in the digestion and absorption of lipids in the small intestine. Inhibition of pancreatic lipase enzyme can reduce dietary fat absorption which will lead to loss of weight and finally result in hypocholesterolemia and hypoglycemia. From the whole plant of Dendrobium senile, a new phenanthrene derivative was isolated, together with seven known compounds, including 2,5,7-trihydroxy-4-methoxyphenanthrene (1), moscatin (2), 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3), moscatilin (4), aloifol I (5), 4,4ʹ,8,8ʹ-tetramethoxy[1,1ʹ-biphenanthrene]-2,2ʹ,7,7ʹ-tetrol (6), 2,2ʹ,7,7ʹ-tetrahydroxy-4,4ʹ-dimethoxy-1,1ʹ-biphenanthrene (7) and bleformin …

Exploring The Dopamine Transporter Utilizing A Two-Pronged Approach With Novel Cathinone Analogs And Mutant Dopamine Transporters, Charles B. Jones Iii

Theses and Dissertations

The dopamine transporter (DAT) is responsible for the removal of the neurotransmitter from the synaptic gap and a therapeutic target for a multitude of drugs. While the ortholog Drosophila melanogaster dopamine transporter (dDAT) and human serotonin transporter (hSERT) have resolved structures, the human dopamine transporter (hDAT) does not. A 3-D computational homology model of hDAT was constructed for the study of molecular interactions with agents within the central binding site (S1) of the transporter.

Synthetic cathiones are a class of abused stimulant drugs that primarily target DAT. Greater than 150 cathinones have been identified on the clandestine market but there …

Development Of Sam-Based Chemical Probes For Methyltransferases, Daniel V. Mongeluzi

Theses and Dissertations

Fig.1. SAM analog for the profiling of MTase activity. A. Chemical structure of probe 1; B. General scheme of the labeling and capture strategy.

A

B

Methylation is a fundamental mechanism used in the biological system to modify the structure and function of biomolecules such as proteins, DNA, RNA, and metabolites.¹ Methyl groups are installed by a large and diverse class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases), which transfer the sulfonium methyl group of SAM to either carbon, nitrogen, oxygen, or other heteroatoms on biomolecules.² Dysregulated MTase activity contributes to numerous diseases, including cancer, metabolic disorders, neurodegenerative diseases. …

Usp <800> Compliance: A Hazardous Drug Safe Handling Ppe Toolkit For Infusion Nurses, Cynthia Huff

Doctor of Nursing Practice (DNP) Projects

Problem: Safety concerns have existed for more than 40 years about how hazardous drug (HD) exposure contributes to long- and short-term adverse health outcomes for healthcare workers (HCWs). Careless handling may cause toxic residues to infiltrate hospital environments and patient care areas, and can even be traced to patients’ homes. New government regulations will require healthcare organizations to minimize exposure risks to HCWs by fully implementing the U.S. Pharmacopeia (USP) Convention Chapter 800: Hazardous Drugs: Handling in Healthcare Settings (USP, 2016) on December 1, 2019. According to Polovich and Olsen (2017), “The implementation of the USP <800> Standards will represent …

Oil/Water Nanoemulsion Biodistribution In Mice Upon Intravenous Administration, Jiayi Chen

Theses and Dissertations

The present study aimed to explore the biodistribution of O/W nanoemulsions (NE) upon intravenous administration. Three NEs were prepared with distinctive droplet sizes: SE (29 ± 1 nm), ME (214 ± 2 nm) and LE (883 ± 16 nm) without overlapping of the size distribution. Kolliphor® HS15 was used as the only surfactant for these three NEs, so that their droplets had similar surface structure. The NEs droplet size was stable under room temperature for minimum 3 days in phosphate buffer saline (PBS) and in mice plasma in vitro for 4-hour at 37°C. A lipophilic fluorescent dye, 1, 1’-dioctadecyl-3, 3, …

Profiling Transcription And Retrotransposition Of Mouse L1 Subfamilies, Lingqi Kong

Electronic Theses and Dissertations

Transposable elements, also called jumping genes, comprise almost 45% of the human genome. In contrast, only 1% of the human genome is protein-coding sequences. The function and advantages of maintaining such massive copies of transposable elements in the human genome are still unclear. Long interspersed element 1 (L1), the most substantial group and the only active autonomous transposable element in the human genome, has revealed its unique roles in many diseases. The insertional mutagenesis induced by L1 retrotransposition events could threaten human genomic stability and generate unexpected mutations. L1 overexpression has been documented in both somatic and germline cells and, …

Pharmacokinetic And Metabolomic Studies Of Standardized Extract Of Centella Asiatica (Eca 233) Capsule In Thai Healthy Volunteers, Phanit Songvut

Chulalongkorn University Theses and Dissertations (Chula ETD)

A well-characterized standardized extract of Centella asiatica (ECa 233) being developed as a phytopharmaceutical product for human use was explored in this clinical study. The first objective of this research was to understand changes in disposition kinetics after oral administration of both the original-formula capsule and a newly-modified enhanced-dissolution capsule of ECa 233. Secondly, this study aimed to investigate alteration of human metabolomes following administration of the modified capsule of ECa 233, using an NMR-based metabolomics approach. For pharmacokinetics, the study involved a phase I clinical trial in twelve healthy Thai volunteers, who each received 250 and 500 mg of …

Ramucirumab: A New Agent For Advanced Or Metastatic Gastric Junction Adenocarcinoma, Adam Smith, Rebecca Worden, Jessica Hoffert, Brendon Rasor, Hannah Stewart, David Koh

Pharmacy and Wellness Review

Ramucirumab (Cyramza®), approved April 21, 2014, is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist with a U.S. Food and Drug Administration (FDA) indication for the treatment of advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. Gastric cancer is a prevalent cancer in the United States with a poor prognosis. The phase 3 trial, REGARD, shows that ramucirumab, when used within four months after the last dose of first-line chemotherapy or six months after the last dose of adjuvant chemotherapy, increases overall survival. Also, ramucirumab has been included in combination therapy, such as in the RAINBOW trial, which demonstrated its effectiveness …

A New Prenylated Isoflavonoid From Limonium Leptophyllum, Asset Dizamatova, Kamila Zhumanova, Galiya E. Zhusupova, Aizhan I. Zhussupova, Radhakrishnan Srivedavyasasri, Mohamed A. Ibrahim, Samir A. Ross

Faculty and Student Publications

© 2019, Mary Ann Liebert, Inc., publishers 2019. Purpose: Cannabidiol (CBD), active component of plant Cannabis sativa, has anti-inflammatory properties that could potentially help treat diabetic retinopathy-induced pain and inflammation. However, CBD is a lipophilic molecule making its topical delivery to back of the eye challenging. This study aims at improving ocular penetration of CBD by means of analog derivatization. Methods: Analogs were designed using various ligands, such as amino acids (AAs) and dicarboxylic acids (DCAs) and their combinations. Select analogs were screened in vitro with respect to their stability in ocular tissue homogenates. Based on in vitro stability, analogs …

Carbapenem-Resistant Enterobacteriaceae Infections: A Review Of Epidemiology And Treatment Options, Julie Harting

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Value Of Universally Available Raw Nmr Data For Transparency, Reproducibility, And Integrity In Natural Product Research., James B. Mcalpine, Shao-Nong Chen, Andrei Kutateladze, John B. Macmillan, Giovanni Appendino, Andersson Barison, Mehdi A. Beniddir, Maique W. Biavatti, Stefan Bluml, Asmaa Boufridi, Mark S. Butler, Robert J. Capon, Young H. Choi, David Coppage, Phillip Crews, Michael T. Crimmins, Marie Csete, Pradeep Dewapriya, Joseph M. Egan, Mary J. Garson, Grégory Genta-Jouve, William H Gerwick, Harald Gross, Mary Kay Harper, Precilia Hermanto, James M. Hook, Luke Hunter, Damien Jeannerat, Nai-Yun Ji, Tyler A. Johnson, David G. I. Kingston, Hiroyuki Koshino, Hsiau-Wei Lee, Guy Lewin, Jie Li, Roger G Linington, Miaomiao Liu, Kerry L Mcphail, Tadeusz F Molinski, Bradley S Moore, Joo-Won Nam, Ram P Neupane, Matthias Niemitz, Jean-Marc Nuzillard, Nicholas H Oberlies, Fernanda M M Ocampos, Guohui Pan, Ronald J Quinn, D Sai Reddy, Jean-Hugues Renault, José Rivera-Chávez, Wolfgang Robien, Carla M Saunders, Thomas J Schmidt, Christoph Seger, Ben Shen, Christoph Steinbeck, Hermann Stuppner, Sonja Sturm, Orazio Taglialatela-Scafati, Dean J Tantillo, Robert Verpoorte, Bin-Gui Wang, Craig M Williams, Philip G Williams, Julien Wist, Jian-Min Yue, Chen Zhang, Zhengren Xu, Charlotte Simmler, David C Lankin, Jonathan Bisson, Guido F Pauli

Natural Sciences and Mathematics | Faculty Scholarship

With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data …

Phytochemical Investigation And Drug Interaction Potential Of Cyanotis Vaga, Ibrahim Almarabi

Electronic Theses and Dissertations

Cyanotis. vaga (Lour.) Schult, & Schult. f. (C. vaga) previously called Tradescantia vaga and Cyanotis barbata, is a perennial herb. It is native to Eastern Asia and Tropical Africa. It has been reported that its decoction reduces fever and enhances well-being. Recently, C. vaga has been used widely for its anabolic effects, due to its richness of ecdysteroids. Even though C. vaga is a commedicinal plant (dietary supplement), there are no reports about its effect on the drug metabolizing enzyme Cytochromes P450 to predict its interaction with concomitantly used medications. In this study, eight ecdysteroids were isolated …

Phytochemicals With Α-Glucosidase Inhibitory Activity From Cissus Javana, Dendrobium Christyanum, Gastrochilus Bellinus And Huberantha Jenkinsii, Htoo Tint San

Chulalongkorn University Theses and Dissertations (Chula ETD)

Phytochemical investigations of Cissus javana DC., Dendrobium christyanum Rchb. f., Gastrochilus bellinus Rchb. f. Kuntze and Huberantha jenkinsii (Hook. f. & Thomson) Chaowasku led to the isolation of twenty-seven compounds, six of which were new naturally occurring compounds. From Cissus javana, three known compounds were isolated, including bergenin, stigmast-4-en-3-one, and β-sitosterol. From Dendrobium christyanum, thirteen known compounds were identified, namely, n-eicosyl trans-ferulate, n-docosyl 4-hydroxy-trans-cinnamate, 4,5-dihydroxy-2-methoxy-9,10-dihydrophenanthrene, moscatilin, aloifol I, gigantol, batatasin III, dendrosinen B, coniferyl aldehyde, methyl haematommate, atraric acid, vanillin and diorcinolic acid. From Gastrochilus bellinus, four new compounds, comprising three phenanthropyrans and a phenanthrene derivative, were isolated and structurally …

Chemical Modifications Of Α-Mangostin For Cytotoxic Study On Lung Cancer Cell Lines, Nan Yadanar Lin Pyae

Chulalongkorn University Theses and Dissertations (Chula ETD)

α-Mangostin is a natural oxygenated and prenylated xanthone, which is mainly isolated from the pericarps of Garcinia mangostana. It possesses numerous pharmacological properties and promising therapeutic effects. However, the limitations of α-mangostin such as highly hydrophobicity and poor bioavailability hider its therapeutic applications. To overcome these drawbacks of α-mangostin, chemical modifications have been performed to discover the improved analogs. Herein, two semi-synthetic approaches to obtain new α-mangostin derivatives were investigated by the modifications of the phenolic hydroxy groups at C-3 and C-6 positions involving Smiles rearrangement to install amine functional groups and the addition reaction of isocyanate to form the …

Research News. Publications, 2018. Volume 2, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period July 1 through December 31, 2018

Developing Of Micellar Drug Carriers For The Treatment Of Breast Cancer Bone Metastasis, Tong Liu

Theses & Dissertations

Breast cancer (BC) remains one of the most frequently diagnosed cancer worldwide. Bone is one of the most common sites and often the first clinical indication of metastatic progression of BC. Current treatments including radiation, surgery, and chemotherapy are rarely curative with limited effect in overall survival. The challenge is true especially for patients with triple-negative BC that are not responsive to receptor-targeted therapy, or patients who had exposure to chemotherapy before and might already gain the resistance to some of the drugs.

Here we took advantage of the aminobisphosphonate, alendronate (ALN), that can bind to the bone mineral efficiently …

Research News. Publications, 2018. Volume 1, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period January 1 through June 30, 2018

Site-Selective Modification Of Peptides And Proteins Via Organocatalyzed Henry Reaction, Zilma Pereira Muneeswaran

Seton Hall University Dissertations and Theses (ETDs)

In this research, peptides and protein containing serine on the N-terminus underwent site-selective modification following organocatalyzed bioconjugation that offered an additional functional group. It was shown that transforming the N-terminus serine to an aldehyde allowed site-specific bioconjugation to occur by utilizing the well-known Henry reaction. This method also grants a safer pathway for bioconjugation utilizing “green-chemistry” and biocompatible conditions. Amino acids and amino acid derived organocatalysts were utilized in the Henry reaction resulting in yields of up to 86 % conversion. Promising preliminary results were achieved in this research using peptides and myoglobin as the bioconjugation targets. Further investigation to …

Next Generation Of Translational Long-Acting Cabotegravir, Tian Zhou

Theses & Dissertations

Recent development of long-acting antiretroviral therapeutic regimens has opened a new chapter for HIV/AIDS management. Cabotegravir (CAB), as one of the very first long-acting antiretroviral regimens, has drawn tremendous attention. However, the remaining challenges include suboptimal dosing intervals, large injection volume, injection site reactions, lack of tissue penetration, etc. As one of the pioneers in this field, our lab was successful in harnessing mononuclear phagocytes as “Trojan horses” for antiretroviral drug delivery and transportation to viral reservoirs. We proposed this targeted delivery strategy could address the limitations of current CAB formulation. To this end, we developed folic acid decorated CAB …

Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activities of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against …

Synthetic Investigation Of Natural Products Causing Dopaminergic Neurodegeneration, Michael John Cunningham

Electronic Theses and Dissertations

The terrestrial organisms Streptomyces venezuelae and Rhaponticum repens produce toxic secondary metabolites that likely function as chemical deterrents. The polyketide SV-6 from S. venezuelae and the sesquiterpene lactone repin from R. repens both produce dose-dependent and selective degeneration of dopaminergic neurons. These molecules represent two possible tools that can be used to explore chemotoxic induction of Parkinson’s disease. In the case of SV-6, a newly isolated metabolite, total synthesis was undertaken to confirm its structure and biological activity. The natural product was produced from methacrolein and Roche ester starting materials that were elaborated to their respective fragments, a vinyl iodide …

Synthesis And Biological Evaluation Of Novel Drug Candidates To Address Drug Resistance In Tuberculosis And Fungal Diseases, Huy Ngo

Theses and Dissertations--Pharmacy

Tuberculosis (TB) and fungal infections are two of the most lethal infectious diseases worldwide due to the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) and fungal strains that can resist the most potent antimicrobial drugs currently employed. Due to the rise of these drug resistant strains, effective treatment options for these two infections are limited. This dissertation aims at exploring novel drug scaffolds to help combat drug resistance in TB and fungal infections.

TB caused by the pathogenic Mtb is, alongside with human immunodeficiency virus acquired immunodeficiency virus (HIV), the deadliest infectious disease worldwide with approximately 2-3 billion people …

Research News. Publications, 2017. Volume 2, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period July 1 through December 31, 2017

Diverse Amide Analogs Of Sulindac For Cancer Treatment And Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivoantitumor activity that was comparable to sulindac in a human colon tumorxenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Identification Of Cdks As Novel Targets Of Aspirin And Its Metabolites: A Potential Role In Cancer Prevention, Rakesh Dachineni

Electronic Theses and Dissertations

Background:
The pursuit of drugs that inhibit cyclin-dependent kinases (CDKs) has been an intense area of research for more than 15 years. Till date, although multiple CDK inhibitors have been identified and few are undergoing clinical trials, only two synthetic drugs have been approved by Food and Drug Administration (FDA) for use in the treatment of cancer. These two drugs are mainly used for the treatment of metastatic breast cancer in combination with other drugs; however they have toxicity associated with their use and extends patients life not more than 24 months. Therefore, there is an urgent need for …

Polymeric Nanocarriers For Delivery Of Small Molecules And Mirnas For The Treatment Of Liver Fibrosis And Pancreatic Cancer, Virender Kumar

Theses & Dissertations

The aim of this thesis is to develop combination therapy of small molecules and miRNAs for treating liver fibrosis and pancreatic cancer. New amphiphilic biodegradable polymers capable of carrying small hydrophobic molecules and hydrophilic anionic nucleic acids were synthesized, characterized and evaluated in vitro and in vivo liver fibrosis and pancreatic cancer mouse models.

In Chapter 1, an overview of liver fibrosis, current treatments and the role of miRNAs in liver fibrosis as well as the design of their delivery systems is given. Further, a general introduction to pancreatic cancer and role of miRNAs in pancreatic cancer is given. In …

Structural And Dynamic Analysis Of Wild And Splice Variants Human Μ-Opiod Receptors In Complex With Morphine And Ibntxa And Human Topoisomerase Ii Alpha Mutational Basis Of Amsacrine Resistance, Safaa Sader

Theses and Dissertations

Morphine prescribing is limited by its high addiction tendency and other serious effects. Recent animal’s biological studies on Mu 6TM splice variants, which mainly include G1, G2 and Mu3, supported a high safety and potency profiles of IBNtxA as potential alternative of Morphine. Nevertheless, there is no high-resolution structures of these 6TM variants, and the detailed structural features and dynamic characteristics of these splice variants remain elusive. We applied homology modeling and MD simulation to probe the structural, dynamic and ligand binding differences between the wild type (7TM) and two major truncated 6TM variants (G1 and G2). MD results underscored …

Biosimilar Naming Conventions: Pharmacist Perceptions And Impact On Confidence In Dispensing Biologics, Daniel M. Tomaszewski

Pharmacy Faculty Articles and Research

BACKGROUND: The approval of the first biosimilar in the United States has placed increased pressure on the FDA to provide guidance on the naming convention that will be assigned to current and future biosimilars. The release of the FDA draft guidance on nonproprietary naming of biosimilars in August 2015 established a naming convention for all biologic products, including biosimilars. However, the draft guidance is nonbinding while the FDA continues to receive input from stakeholders, and it does not address the naming convention that will be used for products designated as interchangeable biologics.

OBJECTIVES: To (a) determine pharmacist perceptions …