Catalytic, Selective, And Stereocontrolled Construction Of C4 Quaternary And Homobenzylic Dihydroisoquinolones By Sp3 C–H Benzylation,
2020
Central Washington University
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,
2020
CUNY Graduate Center
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,
2020
Aga Khan University
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,
2020
Technological University Dublin
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.,
2020
Department of Natural Sciences and Mathematics, Dominican University of California
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,
2020
Southwest University, Chongqing, China
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-HT2A and 5-HT2C 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-HT2A agonist (TCB-2, 0.4 or 4.0 μg/side) or a 5-HT2C 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,
2020
College of Public Health Sciences
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,
2020
Virginia Commonwealth University
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,
2020
VCU, School of Pharmacy
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 …
Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes,
2019
University of Nebraska Medical Center
Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng
Theses & Dissertations
Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …
Computational Studies And Design Of Pparγ And Glut1 Inhibitors,
2019
University of Nebraska Medical Center
Computational Studies And Design Of Pparγ And Glut1 Inhibitors, Suliman Almahmoud
Theses & Dissertations
The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor of the nuclear receptor superfamily that controls the expression of a variety of genes involved in fatty acid metabolism, adipogenesis, and insulin sensitivity. PPARγ is a target for insulin-sensitizing drugs, and it plays a significant function in prostate cancer. PPARγ antagonists have anti-proliferative effects in a broad range of hematopoietic and epithelial cell lines. The ligand binding domain (LBD) of PPARγ is large and has orthosteric and allosteric binding sites. Several PPARγ-ligand co-crystal structures show two bound molecules, one to the orthosteric pocket and a second to the allosteric …
Sustainable Solutions, Fall/Winter 2020, Issue 41,
2019
University of Louisville
Sustainable Solutions, Fall/Winter 2020, Issue 41
Sustain Magazine
No abstract provided.
Environmentally Responsible Land Use, Spring/Summer 2010, Issue 22,
2019
University of Louisville
Environmentally Responsible Land Use, Spring/Summer 2010, Issue 22
Sustain Magazine
No abstract provided.
Sustainable Communities, Fall/Winter 2010, Issue 21,
2019
University of Louisville
Sustainable Communities, Fall/Winter 2010, Issue 21
Sustain Magazine
No abstract provided.
Sustainable Building, Spring/Summer 2009, Issue 20,
2019
University of Louisville
Sustainable Building, Spring/Summer 2009, Issue 20
Sustain Magazine
No abstract provided.
Environmental History, Fall/Winter 2009, Issue 19,
2019
University of Louisville
Environmental History, Fall/Winter 2009, Issue 19
Sustain Magazine
No abstract provided.
Student Research, Spring/Summer 2008, Issue 18,
2019
University of Louisville
Evolving Pollution Prevention, Fall/Winter 2008, Issue 17,
2019
University of Louisville
Evolving Pollution Prevention, Fall/Winter 2008, Issue 17
Sustain Magazine
No abstract provided.
Climate Change, Spring/Summer 2007, Issue 16,
2019
University of Louisville
Our Energy Future, Fall/Winter 2007, Issue 15,
2019
University of Louisville
