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Articles 1 - 30 of 36
Full-Text Articles in Organic Chemicals
A Study Of Awareness Of Antiseptics And Disinfectant Use Among Allied Health Sciences Students And Interns Of A Tertiary Care Hospital, Pooja M, Puneeth A, Sharmi Nm
A Study Of Awareness Of Antiseptics And Disinfectant Use Among Allied Health Sciences Students And Interns Of A Tertiary Care Hospital, Pooja M, Puneeth A, Sharmi Nm
Digital Journal of Clinical Medicine
Background:
Antiseptics and disinfectants are among the most vital tools in infection prevention and control (IPC), especially in healthcare settings where the risk of hospital-acquired infections (HAIs) remains a significant concern. This study aims to assess the awareness and knowledge of antiseptics and disinfectants among Allied Health Sciences (AHS) students and interns, identify knowledge gaps at different stages of training, and recommend educational interventions.
Methods:
This was a cross-sectional, questionnaire-based study conducted among 1st to 3rd-year AHS students and interns at a tertiary care hospital. Data were collected using a validated questionnaire via a Google form after obtaining approval from …
Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner
Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner
Honors Undergraduate Theses
Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.
Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …
Total Synthesis Of The Marine Cytotoxic Mansouramycin And Derivatives, Aditya Dantu, Gabriella L. Madrigal, Neel Gondi, David Osazee, Ahmad Amro, Whard Alsabbagh, Shizue Mito
Total Synthesis Of The Marine Cytotoxic Mansouramycin And Derivatives, Aditya Dantu, Gabriella L. Madrigal, Neel Gondi, David Osazee, Ahmad Amro, Whard Alsabbagh, Shizue Mito
Research Colloquium
Purpose: Isoquinolinequinones are a group of organic compounds which are composed of an isoquinoline fused to a quinone ring. This class of molecules is known to exhibit a wide variety of biological activities, including cytotoxic and antitumor properties. Among the many families of isoquinolinequinones are the Caulibugulones and Mansouramycins, which exhibit anticancer properties and are thus desirable subjects for cancer-related research. They are obtained by isolation from marine bryozoan Caulibugula intermis and marine Streptomyces sp respectively, however these compounds are difficult to extract. Thus, organic synthesis is being explored as a method of obtaining them; this project focuses on the …
Advances In Indole Chemistry: Regiodivergent Annulations And Bridged Azacycle Synthesis, Zachary Tihomir Protich
Advances In Indole Chemistry: Regiodivergent Annulations And Bridged Azacycle Synthesis, Zachary Tihomir Protich
Dartmouth College Ph.D Dissertations
An important aspect for the research and development of new drug therapies is the ability to use modular synthetic methods to rapidly access structurally diverse drug-like building blocks. Nitrogen-containing heterocycles represent one of the most prevalent structural motifs found in pharmaceutical agents and biologically active natural products. However, despite their ubiquity, existing methods for accessing these structures often remain limited in scope, efficiency, and structural diversity, particularly when targeting densely functionalized or sterically demanding scaffolds from simple starting materials.
To address this problem, the research described in this dissertation focuses on the design and development of (3+2) annulation reactions for …
Unplanned Hospitalization Among Advanced Prostate Cancer Patients By Diabetes Status: A Population-Based Study, Amy L. Shaver, Krupa Gandhi, Scott W. Keith, Nikita Nikita, Christopher C. Yang, Felix J. Kim, Hushan Yang, William K. Kelly, Stephen J. Freedland, Grace Lu-Yao
Unplanned Hospitalization Among Advanced Prostate Cancer Patients By Diabetes Status: A Population-Based Study, Amy L. Shaver, Krupa Gandhi, Scott W. Keith, Nikita Nikita, Christopher C. Yang, Felix J. Kim, Hushan Yang, William K. Kelly, Stephen J. Freedland, Grace Lu-Yao
Kimmel Cancer Center Faculty Papers
BACKGROUND: Older adults with advanced prostate cancer and type 2 diabetes mellitus are underrepresented in trials of androgen receptor pathway inhibitors. This study examined changes in unplanned hospitalization rates in patients receiving androgen receptor pathway inhibitors by type 2 diabetes mellitus status and assessed if unplanned hospitalization varies according to androgen receptor pathway inhibitors.
METHODS: This population-based study of advanced prostate cancer patients aged older than 66 years used Surveillance, Epidemiology, and End Results-Medicare data. Prepost androgen receptor pathway inhibitor initiation changes and androgen receptor pathway inhibitor differences in unplanned hospitalization rates were estimated by adjusted incidence rate ratio with …
A Rare Case Of Diffuse Alveolar Hemorrhage In The Setting Of Iga Nephropathy, Vasculitis And Atypical Hemolytic Uremic Syndrome In A Previously Healthy Young Adult, Karl Schlicht, Nancy Kaura
A Rare Case Of Diffuse Alveolar Hemorrhage In The Setting Of Iga Nephropathy, Vasculitis And Atypical Hemolytic Uremic Syndrome In A Previously Healthy Young Adult, Karl Schlicht, Nancy Kaura
Rowan-Virtua Research Day
IgA Nephropathy, also known as Berger disease, can precipitate acute renal failure in patients. IgA Nephropathy (IgAN) is deposition of protein from IgA into the renal tissue with subsequent renal dysfunction. IgA vasculitis (IgAV) is another condition where similarly the protein of IgA is deposited into the vessels. There are some cases of co-existing atypical hemolytic uremic syndrome (aHUS) with IgAN. However, rare combinations seen with all three IgAN, IgAV, and aHUS without any pre-existing conditions nor medical history. Patients that develop any one of these conditions are looking at life long changes with hemodialysis (HD) and organ transplants being …
Fluorine-Containing Isosteres Enable A Structure-Activity Relationship Study Of Gingerol Derivatives, Shelby Cooper, Diarta Kabashi, Marlin Yacoub, Jessica Molen, Osman Farhan, Christina Farley, Samantha Yencha, Michelle Figueiredo, Nidheesh Phadnis, Wynter Henry, Julian Harris, Frank Wilkinson, John Milligan
Fluorine-Containing Isosteres Enable A Structure-Activity Relationship Study Of Gingerol Derivatives, Shelby Cooper, Diarta Kabashi, Marlin Yacoub, Jessica Molen, Osman Farhan, Christina Farley, Samantha Yencha, Michelle Figueiredo, Nidheesh Phadnis, Wynter Henry, Julian Harris, Frank Wilkinson, John Milligan
College of Life Sciences Faculty Papers
A series of fluorinated and non-fluorinated [6]-gingerol, [6]-paradol, [6]-shogaol and ferulate derivatives were synthesized. Testing these analogs in anti-proliferation assays with MCF-7, A549, HCT-116 and HEK-293 cell lines provided insight into the structural features that contribute to the anti-proliferative activity of naturally occurring ginger constituents. In particular, the use of both vinyl and alkyl trifluoromethyl isosteres allowed us to evaluate the structure-activity impact of the enone motif found in shogaols. Our results indicate that enone-containing derivatives have a higher potency, suggesting the conjugated enone motif characteristic of shogaols may be primarily responsible for the anti-cancer activity of the broader natural …
Nutritional, Phytochemical, And Antimicrobial Properties Of Carica Papaya Leaves: Implications For Health Benefits And Food Applications, Rajni Choudhary, Ravinder Kaushik, Ansab Akhtar, Suvendu Manna, Jyoti Sharma, Aarti Bains
Nutritional, Phytochemical, And Antimicrobial Properties Of Carica Papaya Leaves: Implications For Health Benefits And Food Applications, Rajni Choudhary, Ravinder Kaushik, Ansab Akhtar, Suvendu Manna, Jyoti Sharma, Aarti Bains
School of Medicine Faculty Publications
BACKGROUND: Papaya leaves (PLs) are known for their therapeutic benefits and traditional use in treating inflammation, infections, and various health conditions. Rich in bioactive compounds, PLs are studied for their potential applications in functional foods. This study analyzed their nutritional, phytochemical, structural, thermal, and antimicrobial properties to evaluate their role as a health-promoting ingredient. METHODS: Phytochemicals were quantified spectrophotometrically and identified via GC-MS. Antioxidant activity was assessed using DPPH and FRAP assays. Mineral content was determined using ICP-OES. Structural and thermal properties were evaluated using FTIR, XRD, and calorimetry, and antimicrobial activity was tested via the agar well diffusion method. …
Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don
Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don
Theses and Dissertations
In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.
For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …
Beta-Blocker Use In Patients Undergoing Non-Cardiac Surgery: A Systematic Review And Meta-Analysis, Doménica Herrera Hernández, Bárbara Abreu, Tania S. Xiao, Andreina Rojas, Kevin López Romero, Valentina Contreras, Sol Villa Nogueyra, Zulma Sosa, Samantha M. Alvarez, Camila Sánchez Cruz, Ernesto Calderón Martinez
Beta-Blocker Use In Patients Undergoing Non-Cardiac Surgery: A Systematic Review And Meta-Analysis, Doménica Herrera Hernández, Bárbara Abreu, Tania S. Xiao, Andreina Rojas, Kevin López Romero, Valentina Contreras, Sol Villa Nogueyra, Zulma Sosa, Samantha M. Alvarez, Camila Sánchez Cruz, Ernesto Calderón Martinez
Department of Radiology Faculty Papers
BACKGROUND: The use of beta-blockers in the perioperative period has been widely investigated due to their potential to reduce the risk of major adverse cardiovascular and cerebrovascular events (MACCE) and mortality; yet their overall impact on various postoperative outcomes remains debated. This study constitutes a systematic review and meta-analysis of the impact of beta-blockers on mortality, MI, stroke, and other adverse effects such as hypotension and bradycardia in patients undergoing non-cardiac surgery.
METHODS: A comprehensive systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Searches were performed across PubMed, Cochrane, Web of Science, Scopus, EMBASE, and CINAHL databases; …
An Integrative Review Of The Absorption Of Fda-Approved Chemical Sunscreen Filters Into The Blood, Srinidhi Banala, Samrat Gollapudi, Abhiram Gollapudi, Bhaumik Patel
An Integrative Review Of The Absorption Of Fda-Approved Chemical Sunscreen Filters Into The Blood, Srinidhi Banala, Samrat Gollapudi, Abhiram Gollapudi, Bhaumik Patel
Rowan-Virtua Research Day
Introduction: This integrative review examines the absorption of FDA-approved chemical sunscreen filters, specifically avobenzone and oxybenzone, into the bloodstream. The study aims to compare the levels of absorption and potential health effects of systemic exposure to these sunscreen ingredients in the United States.
Methods: The researchers conducted a literature search of 57 articles, of which 15 were used for the review. Inclusion criteria focused on studies discussing absorption levels of avobenzone and oxybenzone, as well as methods of absorption into the bloodstream. Exclusion criteria included sunscreen ingredients not approved in the United States, non-English studies, and studies on methods to …
Exogenous Exposure To Dihydroxyacetone Mimics High Fructose Induced Oxidative Stress And Mitochondrial Dysfunction, Raj Mehta
Honors Theses
Dihydroxyacetone (DHA) is a three-carbon sugar that is the active ingredient in sunless tanning products and a by-product of electronic cigarette (e-cigarette) combustion. Increased use of sunless tanning products and e-cigarettes has elevated exposures to DHA through inhalation and absorption. Studies have confirmed that DHA is rapidly absorbed into cells and can enter into metabolic pathways following phosphorylation to dihydroxyacetone phosphate (DHAP), a product of fructose metabolism. Recent reports have suggested metabolic imbalance and cellular stress results from DHA exposures. However, the impact of elevated exposure to DHA on human health is currently under-investigated. We propose that exogenous exposures to …
The Role Of Alpha-2 Agonists For Attention Deficit Hyperactivity Disorder In Children: A Review, Elisa E. Neuchat, Brooke E. Bocklud, Kali Kingsley, William T. Barham, Patrick M. Luther, Shahab Ahmadzadeh, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye
The Role Of Alpha-2 Agonists For Attention Deficit Hyperactivity Disorder In Children: A Review, Elisa E. Neuchat, Brooke E. Bocklud, Kali Kingsley, William T. Barham, Patrick M. Luther, Shahab Ahmadzadeh, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye
School of Medicine Faculty Publications
Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases. However, these medications’ long-term safety and efficacy remain uncertain, with a lack …
Comparison Of Clinical And Radiographic Efficacy Of Particles Versus Nbca/Onyx In Middle Meningeal Artery Embolization For Chronic Subdural Hematoma, Jane Khalife, Mohamed Salem, Victoria Wong Murray, Allen Karimov, Brian Jankowitz, Jan Karl Burkhardt, Hamza Shaikh, Daniel Tonetti, Pratit Patel, Tudor Jovin, Ajith Thomas
Comparison Of Clinical And Radiographic Efficacy Of Particles Versus Nbca/Onyx In Middle Meningeal Artery Embolization For Chronic Subdural Hematoma, Jane Khalife, Mohamed Salem, Victoria Wong Murray, Allen Karimov, Brian Jankowitz, Jan Karl Burkhardt, Hamza Shaikh, Daniel Tonetti, Pratit Patel, Tudor Jovin, Ajith Thomas
Rowan-Virtua Research Day
Different embolic materials are utilized in MMA embolization of chronic subdural hematoma per operators’ discretion. We aim to compare the clinical and radiographic efficacy of different embolic materials in a pooled retrospective cohort of two US centers.
Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters
Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters
Undergraduate Honors Theses
Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD+) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD+ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPRmt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD+ and through increasing levels …
Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista
Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista
Selected Honors Theses
Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …
Drug-Facilitated Sexual Assault At The University Of Arkansas, Barrett Weidman
Drug-Facilitated Sexual Assault At The University Of Arkansas, Barrett Weidman
Chemical Engineering Undergraduate Honors Theses
This work was written to fulfill two main purposes. First, to help survivors of Drug-Facilitated Sexual Assault (DFSA) process their experience by compiling the toxicological, pharmacological, and distribution of the three most used date-rape drugs. Second, to gauge the knowledge and interest of University of Arkansas students regarding drug impairments, sexual assault education, and bystander intervention training. A survey was conducted for the latter and revealed that 91.6% of students believe the University’s existing sexual assault prevention education and bystander intervention training have room for improvement. Also, 37.1% of students who have received this education report that the programming does …
Antibacterial Activity, Structure-Activity Relationships, And Scale-Up Reaction Of 1,3,4-Oxadiazoles, Olivia Marie Smith
Antibacterial Activity, Structure-Activity Relationships, And Scale-Up Reaction Of 1,3,4-Oxadiazoles, Olivia Marie Smith
Undergraduate Honors Thesis Projects
Oxadiazoles are compounds in the field of organic chemistry that have been gathering interest in the medicinal chemistry and microbiology communities for their biological properties, which range from anti-inflammatory agents, to chemotherapy drugs, to antibiotics. The synthesis of oxadiazoles can be difficult due to the expensive and complex nature of the techniques used as well as the volatile reagents and elevated temperatures that are often required in organic synthesis. The Grote lab has recently developed a new method for the synthesis of 1,3,4-oxadiazoles under mild conditions. The goals of this thesis were thus twofold: to develop a viable scale-up procedure …
Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw
Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw
Electronic Theses and Dissertations
Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to PM2.5 is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD is less clear. Overall, this work aimed to examine the effect of pollutants with lesser documented effects on cardiovascular disease using a multi-pronged approach to exposure assessment. The three aims were to examine the relationship between county-level toxic chemical releases and CVD mortality in the contiguous United States between 2002 and 2012, to assess the relationship between individual-level VOC metabolites and vascular function, and to build multipollutant …
Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters
Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters
Undergraduate Honors Theses
The nicotinamide riboside (NR) form of vitamin B3and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B3are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD+decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD+levels. BHB is naturally produced by the body when individuals fast …
Understanding Structure-Activity Relationship Of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate, Barkha J. Yadav
Understanding Structure-Activity Relationship Of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate, Barkha J. Yadav
Theses and Dissertations
Synthetic cathinones are stimulant drugs of abuse that act at monoamine transporters e.g. the dopamine transporter (DAT) as releasing agents or as reuptake inhibitors. More than >150 new synthetic cathinones have emerged on the clandestine market and have attracted considerable attention from the medical and law enforcement communities.
threo-Methylphenidate (tMP) is an FDA approved drug for the treatment of ADHD and narcolepsy, which also acts as a DAT reuptake inhibitor and is widely abused. tMP and synthetic cathinones share some structural similarities and extensive structure-activity relationship (SAR) studies on tMP have been conducted. However, much less is known about the …
Retrospective Review Of Alternative Antibiotic Use In Patients With A Reported Penicillin Allergy At A Community Hospital, Rita Chamoun, Monica Tadros, Amy Montes, Heidi Clarke, Radhan Gopalani
Retrospective Review Of Alternative Antibiotic Use In Patients With A Reported Penicillin Allergy At A Community Hospital, Rita Chamoun, Monica Tadros, Amy Montes, Heidi Clarke, Radhan Gopalani
All Publications
No abstract provided.
A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang
A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang
Pharmacy Faculty Articles and Research
Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …
Towards The Development Of A Novel Dna Binding Fluorescent Cell Stain; An Analysis Of Common Dna Dyes And Their Applications, Lauren Kapteyn
Towards The Development Of A Novel Dna Binding Fluorescent Cell Stain; An Analysis Of Common Dna Dyes And Their Applications, Lauren Kapteyn
Senior Honors Theses
Fluorescent deoxyribonucleic acid (DNA) stains that permeate cells are used to observe cellular processes in vivo, making them valuable tools. For the proposal of a new stain, ethidium bromide, cyanine dyes, Hoechst stains, macarpine, DAPI and DRAQ5 are first examined. Features contributing to DNA binding mechanism, toxicity, and cell membrane transport are analyzed for these compounds. The mechanism of DNA binding contributes to the toxicity of the compound. For dyes with well-understood transport mechanisms, multi-drug protein transporters are vital players, though this remains an area for ongoing research as many mechanisms are not well studied. A novel anthraquinone-based compound …
Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker
Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker
All Master's Theses
The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …
Nitrogen And Phosphorus Availability From Various Composted Wastes For Use In Irish Agriculture And Horticulture, Alan Lee
Doctoral
Current environmental EU legislation promotes recycling and recovery from organic waste products. Compost has been identified as an alternative to inorganic fertilisers and animal slurries as a nutrient source for crop plants. This study aimed to investigate nitrogen (N) and phosphorus (P) availability from various composted waste through detailed characterisations, complemented by short term lab incubations and long term plant growth experiments. Twenty-five composts were selected and classified by their groups. The composts were characterised by multiple different analytical techniques. Two incubation studies were conducted. One investigating N and P mineralisation potential of the composts and the second on the …
Effects Of Nox-1 Inhibition On Real-Time Blood Nitric Oxide And Hydrogen Peroxide In Acute Hyperglycemia, Ashley Mawhinney
Effects Of Nox-1 Inhibition On Real-Time Blood Nitric Oxide And Hydrogen Peroxide In Acute Hyperglycemia, Ashley Mawhinney
PCOM Biomedical Studies Student Scholarship
Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H2O2). Endothelial-derived NO can be significantly reduced by increased SO/H2O2 in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NADPH oxidase isoform 1 (NOX1) is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. This hypothesis was tested by measuring blood NO and H2O2 levels in …
Synthesis And Biochemical Evaluation Of 3-Phenoxy-1,4-Diarylazetidin-2-Ones As Tubulin-Targeting Antitumor Agents, Thomas F. Greene, Shu Wang, Lisa M. Greene, Seema M. Nathwani, Jade K. Pollock, Azizah M. Malebari, Thomas Mccabe, Brendan Twamley, Niamh O'Boyle, Daniela M. Zisterer, Mary J. Meegan
Synthesis And Biochemical Evaluation Of 3-Phenoxy-1,4-Diarylazetidin-2-Ones As Tubulin-Targeting Antitumor Agents, Thomas F. Greene, Shu Wang, Lisa M. Greene, Seema M. Nathwani, Jade K. Pollock, Azizah M. Malebari, Thomas Mccabe, Brendan Twamley, Niamh O'Boyle, Daniela M. Zisterer, Mary J. Meegan
Articles
Structure-activity relationships for a series of 3-phenoxy-1,4-diarylazetidin-2-ones were investigated leading to the discovery of a number of potent antiproliferative compounds, including trans-4-(3-hydroxy-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (78b) and trans-4-(3-amino-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (90b). X-ray crystallography studies indicate the potential importance of the torsional angle between the 1-phenyl ‘A’ ring and 4-phenyl ‘B’ ring for potent antiproliferative activity, and that a trans configuration between the 3-phenoxy and 4-phenyl rings is generally optimal. These compounds displayed IC50 values of 38 nM and 19 nM respectively in MCF-7 breast cancer cells, inhibited the polymerization of isolated tubulin in vitro, disrupted the microtubular …
Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle
Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle
Articles
Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and Western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerised when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, …
Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown
Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown
Theses and Dissertations--Neuroscience
The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …