Digital Commons Network^™

Case 59: Inhibition Of Enzymes Involved In Steroid Synthesis: Implications In Diabetes Treatment, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

Drugs used to increase insulin sensitivity may also inhibit enzymes involved in steroid synthesis. Prior to this investigation, it was uncertain whether the drugs inhibited the enzymes directly or whether the decrease in androgen synthesis observed during treatment was a secondary effect.

Cardiac Myosin-Specific Autoimmune T Cells Contribute To Immune-Checkpoint-Inhibitor-Associated Myocarditis, Johns Hopkins University School Of Medicine, Johns Hopkins University Bloomberg School Of Public Health, Johns Hopkins University Whiting School Of Engineering, Ninaad Lasrado, Jay Reddy, Daniela Ciháková

School of Veterinary and Biomedical Sciences: Faculty Publications

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased …

Cardiac Myosin-Specific Autoimmune T Cells Contribute To Immune-Checkpoint-Inhibitor-Associated Myocarditis, Taejoon Won, Hannah M. Kalinoski, Megan K. Wood, David M. Hughes, Camille M. Jaime, Paul Delgado, Monica V. Talor, Ninaad Lasrado, Jay Reddy, Daniela Čiháková

Jay Reddy Publications

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased …

The Assembly Of Mammalian Swi/Snfchromatin Remodeling Complexes Is Regulated By Lysine-Methylation Dependent Proteolysis, Pengfei Guo, Nam Hoang, Joseph Sanchez, Elaine H. Zhang, Keshari Rajawasam, Kristiana Trinidad, Hong Sun, Hui Zhang

Chemistry and Biochemistry Faculty Research

The assembly of mammalian SWI/SNF chromatin remodeling complexes is developmentally programed, and loss/mutations of SWI/SNF subunits alter the levels of other components through proteolysis, causing cancers. Here, we show that mouse Lsd1/Kdm1a deletion causes dramatic dissolution of SWI/SNF complexes and that LSD1 demethylates the methylated lysine residues in SMARCC1 and SMARCC2 to preserve the structural integrity of SWI/SNF complexes. The methylated SMARCC1/SMARCC2 are targeted for proteolysis by L3MBTL3 and the CRL4DCAF5 ubiquitin ligase complex. We identify SMARCC1 as the critical target of LSD1 and L3MBTL3 to maintain the pluripotency and self-renewal of embryonic stem cells. L3MBTL3 also regulates SMARCC1/SMARCC2 proteolysis …

Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila

Dissertations

Organic synthesis has been significantly advanced with the employment of transition metal complexes. The discovery of transition metal catalysts provided the synthetic community with powerful tools for accelerating reactions and making them more selective and efficient. Many chemical reactions do not happen without a catalyst.

Iron-based catalysts have several advantages for the chemical industry because it is a non-toxic and ecologically friendly metal. Our group previously found that ferrocenium cations with a 3+ oxidation state of iron-catalyzed propargylic substitution reactions at low temperatures. The sandwich structure of ferrocenes allows substituents to be introduced on the cyclopentadienyl rings, which allows for …

Esterase Mediated Insecticide Resistance In The Southern House Mosquito, Culex Quinquefasciatus, Vivek Pokhrel

LSU Doctoral Dissertations

Much is known about the development of insecticide resistance associated with targeted application against insect populations. However, off-target selection by applications of insecticides in agricultural and residential sites also impacts development of insecticide resistance and is understudied. Similarly, the impact of selecting one life stage of mosquitoes on the insecticide susceptibility of different life stages is largely unknown. The first part of this study shows that susceptibility to chlorantraniliprole, which is applied in rice and sugarcane fields in LA, decreased (5.7 to12-fold) in populations of Culex quinquefasciatus collected from near these fields compared to a reference field strain. In addition, …

The Childhood Acute Illness And Nutrition (Chain) Network Nested Case-Cohort Study Protocol: A Multi-Omics Approach To Understanding Mortality Among Children In Sub-Saharan Africa And South Asia, James M. Njunge, Kirkby Tickell, Abdoulaye Hama Diallo, Abu Sadat Mohammad Sayeem Bin Shahi, Md Amran Gazi, Ali Faisal Saleem, Zaubina Kazi, Syed Ali, Caroline Tigoi, Ezekiel Mupere

Department of Paediatrics and Child Health

Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach.
Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and …

Occurrence Of Kanamycin-Resistant Bacteria Relative To Anthropogenic Pollution Along Richland Creek In Nashville, Tn​, Jolene Ho Mach, Annie Le, Brandon Torres Ramirez

Science University Research Symposium (SURS)

The overuse of antibiotics has caused an increase in antibiotic-resistant (AR) bacteria, which is a serious public health concern. Previous studies showed a significant correlation between anthropogenic pollution and AR bacteria. This project aims to identify AR bacteria in Richland Creek relative to local anthropogenic pollution. Water samples were collected at four locations along Richland Creek in Nashville, Tennessee. Bacteria resistant to the antibiotic kanamycin were isolated from the water samples, identified to genera using DNA barcoding, and compared among the sites. We expect to see a greater abundance and diversity of kanamycin-resistant bacteria closer to the end than near …

Nucleobase-Modified Nucleosides And Nucleotides: Applications In Biochemistry, Synthetic Biology, And Drug Discovery, Anthony J. Berdis

Chemistry Faculty Publications

DNA is often referred to as the "molecule of life " since it contains the genetic blueprint for all forms of life on this planet. The core building blocks composing DNA are deoxynucleotides. While the deoxyribose sugar and phosphate group are ubiquitous, it is the composition and spatial arrangement of the four natural nucleobases, adenine (A), cytosine (C), guanine (G), and thymine (T), that provide diversity in the coding information present in DNA. The ability of DNA to function as the genetic blueprint has historically been attributed to the formation of proper hydrogen bonding interactions made between complementary nucleobases. However, …

College Of Natural Sciences Newsletter, September & October 2022, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 3, Issue 6

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 3 Midwest Regional ACS Meeting
Page 4 North Central ASM Meeting
Page 5 Geography Department Travel
Page 6-7 Media Coverage of CNS
Page 7 REMAST Program at SDState receives national spotlight
Page 8 Celebrating the lives of those who touched the College
Page 9 Innovative Learning Spaces
Page 10 Open PRAIRIE Data
Page 11 2022 CNS Scholarship Brunch
Page 12-14 Fall 2022 Outreach Events

Regulation Of Tissue Mechanics And Adherens Junctions By Small Gtpase Rhoa During Drosophila Embryogenesis, Hanqing Guo

Dartmouth College Ph.D Dissertations

Actomyosin contractility plays an important role at both the cell and tissue level during developments. In this study, we developed an optogenetic tool that can acutely inhibit actomyosin contractility by targeting its main activator Rho1. This optogenetic tool can achieve myosin inhibition within one minute and thus enable further dissection of actomyosin function in development. In my first two projects, I used Drosophila mesoderm invagination (also known as ventral furrow formation) as a model to study epithelial folding, a fundamental mechanism for constructing complex 3D tissues. Apical constriction mediated by actomyosin contractility is a common mechanism for epithelial folding. However, …

Modifications Of Cellulose-Based Biomaterials For Biomedical Applications, Nour Fatema, Ruben Michael Ceballos, Chenguang Fan

Chemistry & Biochemistry Faculty Publications and Presentations

Cellulose is one of the most abundant organic compounds in nature and is available from diverse sources. Cellulose features tunable properties, making it a promising substrate for biomaterial development. In this review, we highlight advances in the physical processes and chemical modifications of cellulose that enhance its properties for use as a biomaterial. Three cellulosic products are discussed, including nanofibrillated, nanocrystalline, and bacterial cellulose, with a focus on how each may serve as a platform for the development of advanced cellulose-based biomaterials for Biomedical applications. In addition to associating mechanical and chemical properties of cellulosic materials to specific applications, a …

Successful Use Of Continuous Erector Spinae Plane Blocks In A Patient With Variant Angina After Large Ventral Hernia Repair, Alexandra L Belfar, Yi Deng, Raymond C Yu, Annas Sabbagh

Faculty, Staff and Students Publications

Coronary artery spasm constitutes the primary underlying pathology of variant angina. Because provocation of coronary artery spasm may occur with both excess sympathetic and excess parasympathetic stimulation, patients with this disorder have extremely limited options for perioperative pain control. This is especially true for procedures involving extensive abdominal incision/manipulation. Whereas neuraxial analgesia might otherwise be appropriate in these cases, several studies have demonstrated that coronary artery spasm can occur as a result of epidural placement, and therefore, that this may not be an optimal choice for patients with variant angina. This report discusses the case of a patient with a …

Clearance Of Hiv-1 Or Siv Reservoirs By Promotion Of Apoptosis And Inhibition Of Autophagy: Targeting Intracellular Molecules In Cure-Directed Strategies, Min Chen, Min Li, Marietta M Budai, Andrew P Rice, Jason T Kimata, Mahesh Mohan, Jin Wang

Faculty, Staff and Students Publications

The reservoirs of the HIV display cellular properties resembling long-lived immune memory cells that could be exploited for viral clearance. Our interest in developing a cure for HIV stems from the studies of immunologic memory against infections. We and others have found that long-lived immune memory cells employ prosurvival autophagy and antiapoptotic mechanisms to protect their longevity. Here, we describe the rationale for the development of an approach to clear HIV-1 by selective elimination of host cells harboring replication-competent HIV (SECH). While reactivation of HIV-1 in the host cells with latency reversing agents (LRAs) induces viral gene expression leading to …

Participation In A Longitudinal Seminar Series Increases Medical Student Engagement With The Covid-19 Pandemic, Katherine M Naeger, Kaelyn C Cummins, Prathit A Kulkarni

Faculty, Staff and Students Publications

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic required a multifaceted response by healthcare professionals. Medical students played only a limited role in the early response, resulting in feelings of disengagement. The authors developed a discussion-based elective course reviewing the COVID-19 response to address this gap in medical student education.

METHODS: Preclinical medical students enrolled in this elective participated in weekly virtual interactive seminars led by expert faculty members. Students completed a final survey quantifying their understanding of the overall COVID-19 response, knowledge of its individual facets, and their feelings of personal engagement on a Likert scale from 1 to 5, …

The Effect Of Licogliflozin (Sglt1/2 Inhibitor) On Diabetes And Cardiac Complications, Alanoud Gharib Alblooshi

Theses

Diabetes mellitus (DM) is a chronic endocrine disease affecting millions of people worldwide. In spite of the advances made in the management of DM, poor glycemic control and diabetes complications are still very common. There is a continuous search for new and more effective drugs to treat DM. One of the drugs currently in clinical trials for the treatment of DM is licogliflozin (LIK066), a dual SGLT1/2 inhibitor, which can be used to treat obesity and diabetes. LIK066 inhibits glucose reabsorption in the kidney and small intestine, thereby reducing hyperglycemia. This study aims to investigate the efficacy of licogliflozin on …

Distribution Of Erm Proteins In The Stomach Mucosa Of Normal And Diabetic Rats, Asmaa Salem Al Sereidi

Theses

Diabetes mellitus (DM), or simply diabetes, refers to a group of metabolic disorders that include a variety of diseases that disrupt our body's metabolism. The long-term uncontrolled disease can lead to stomach complications such as gastroparesis, as well as disruption in several proteins, such as ERM (Ezrin, radixin, moesin) proteins. ERM proteins are three proteins that are structurally and functionally related. ERM proteins have molecular masses of 82, 80, and 75 kDa, respectively. Ezrin is highly expressed in the stomach, especially in parietal cells that secrete gastric acid. ERM proteins function as scaffolding proteins in lipid rafts and granule trafficking …

To Be Or Not To Be: A Tale Of Staphylococcal Gpsb, Lauren R. Hammond

USF Tampa Graduate Theses and Dissertations

There are two big drivers motivating studies into bacterial cell division. The first is a desire to understand life around us. One of the defining characteristics of life is the ability for a cell to grow and divide, and without in-depth knowledge of this process, we cannot truly understand the complexities that allow for life on this planet. The second motivator is to identify new drug targets in the ongoing fight against antimicrobial resistance. Many infectious organisms have become resistant to commonly used antibiotics, and the bacterial cell division machinery is a largely untapped essential process with many potential therapeutic …

Lord Of The Z-Rings: Uncovering The Role Of Mraz And Ftsl In Bacillus Subtilis Cell Division, Maria Louise White

USF Tampa Graduate Theses and Dissertations

Cell division is a complex and highly orchestrated process that requires careful coordination. The process of cell division in prokaryotes primarily occurs via binary fission, where one mother cell becomes two genetically identically and equally sized daughter cells. In most bacteria a key protein, FtsZ, forms a FtsZ ring (Z-ring) to mark the division site and recruit proteins involved in cytokinesis. Whilst much has been learned about the contents and assembly of the divisome in model organisms such as Escherichia coli and Bacillus subtilis factors governing the regulation of divisome are much more poorly understood. …

Using The Embl-Ebi Clustal Omega Tool To Calculate Diversity Of Heavy Chain Phage-Display Libraries, Michael Bodri, Shane A. Webb

Georgia Journal of Science

Here we show that traditional Sanger sequencing combined with analysis tools available from the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), specifically EMBOSS Transeq and Clustal Omega, is extremely effective in the analysis of naïve phage display antibody libraries for the determination of library size and diversity. The free tools are easy to use and require little manipulation of reads by hand, allowing analysis to be performed on a standard personal computer. Utilization of this technique has applicability to researchers with limited access to deep sequencing. The primary drawback to this analysis methodology is that antibodies with particular molecular or …

Enhancing Production Of Functional Proteins In Plant Cell Culture Through Cellular Engineering And Rational Protein Design, Uddhab Karki

Student Theses and Dissertations

Plant cell culture is emerging as a promising alternative bioproduction platform for valuable proteins due to its low cost of production, safety (free from animal pathogen contamination) and ease of scale-up. However, there are common challenges for commercialization, including low protein yields, difficulty in cryopreservation, and non-human glycosylation, etc. This research project addresses the overarching research hypothesis that strategically modifying the plant cell genome using CRISPR/Cas9 technology and rationally designing protein molecules by fusing with a functional module enhance the production of protein in plant cell culture and improve protein function. There are two specific aims addressed in this project: …

Loss Of Non-Motor Kinesin Kif26a Causes Congenital Brain Malformations Via Dysregulated Neuronal Migration And Axonal Growth As Well As Apoptosis, Xuyu Qian, Ellen M Degennaro, Maya Talukdar, Shyam K Akula, Abbe Lai, Diane D Shao, Dilenny Gonzalez, Jack H Marciano, Richard S Smith, Norma K Hylton, Edward Yang, J Fernando Bazan, Lee Barrett, Rebecca C Yeh, R Sean Hill, Samantha G Beck, Aoi Otani, Jolly Angad, Tadahiro Mitani, Jennifer E Posey, Davut Pehlivan, Daniel Calame, Hatip Aydin, Osman Yesilbas, Kendall C Parks, Emanuela Argilli, Eleina England, Kiho Im, Ajay Taranath, Hamish S Scott, Christopher P Barnett, Peer Arts, Elliott H Sherr, James R Lupski, Christopher A Walsh

Faculty, Staff and Students Publications

Kinesins are canonical molecular motors but can also function as modulators of intracellular signaling. KIF26A, an unconventional kinesin that lacks motor activity, inhibits growth-factor-receptor-bound protein 2 (GRB2)- and focal adhesion kinase (FAK)-dependent signal transduction, but its functions in the brain have not been characterized. We report a patient cohort with biallelic loss-of-function variants in KIF26A, exhibiting a spectrum of congenital brain malformations. In the developing brain, KIF26A is preferentially expressed during early- and mid-gestation in excitatory neurons. Combining mice and human iPSC-derived organoid models, we discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and …

Inhibiting Glutamine Utilization Creates A Synthetic Lethality For Suppression Of Atp Citrate Lyase In Kras-Driven Cancer Cells, Ahmet Hatipoglu, Deepak Menon, Talia Levy, Maria A. Frias, David A. Foster

Publications and Research

Metabolic reprogramming is now considered a hallmark of cancer cells. KRas-driven cancer cells use glutaminolysis to generate the tricarboxylic acid cycle intermediate α -ketoglutarate via a transamination reaction between glutamate and oxaloacetate. We reported previously that exogenously supplied unsaturated fatty acids could be used to synthesize phosphatidic acid–a lipid second messenger that activates both mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTOR complex 2 (mTORC2). A key target of mTORC2 is Akt–a kinase that promotes survival and regulates cell metabolism. We report here that mono- unsaturated oleic acid stimulates the phosphoryla tion of ATP citrate lyase (ACLY) at …

Whole Genome Sequencing Of Moraxella Bovis Strains From North America Reveals Two Genotypes With Different Genetic Determinants, Emily L. Wynn, Matthew M. Hille, John Dustin Loy, Gennie Schuller, Kristen L. Kuhn, Aaron M. Dickey, James L. Bono, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Moraxella bovis and Moraxella bovoculi both associate with infectious bovine keratoconjunctivitis (IBK), an economically significant and painful ocular disease that affects cattle worldwide. There are two genotypes of M. bovoculi (genotypes 1 and 2) that differ in their gene content and potential virulence factors, although neither have been experimentally shown to cause IBK. M. bovis is a causative IBK agent, however, not all strains carry a complete assortment of known virulence factors. The goals of this study were to determine the population structure and depth of M. bovis genomic diversity, and to compare core and accessory genes and …

Genetic Inhibition Of Nuclear Factor Of Activated T-Cell C2 Prevents Atrial Fibrillation In Crem Transgenic Mice, Li Ni, Satadru K Lahiri, Jiali Nie, Xiaolu Pan, Issam Abu-Taha, Julia O Reynolds, Hannah M Campbell, Haihao Wang, Markus Kamler, Wilhelm Schmitz, Frank Ulrich Müller, Na Li, Xiang Wei, Dao Wen Wang, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

AIMS: Abnormal intracellular calcium (Ca2+) handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signalling pathway contributes to atrial remodelling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models.

METHODS AND RESULTS: Expression levels of NFATc1-c4 isoforms were assessed by quantitative reverse transcription-polymerase chain reaction in right atrial appendages from patients with chronic AF (cAF). NFATc1 and NFATc2 mRNA levels were elevated in cAF patients compared with those in normal sinus …

Control Of Ribosomal Rna Synthesis By Hematopoietic Transcription Factors, Charles Antony, Subin S George, Justin Blum, Patrick Somers, Chelsea L Thorsheim, Dexter J Wu-Corts, Yuxi Ai, Long Gao, Kaosheng Lv, Michel G Tremblay, Tom Moss, Kai Tan, Jeremy E Wilusz, Austen R D Ganley, Maxim Pimkin, Vikram R Paralkar

Faculty, Staff and Students Publications

Ribosomal RNAs (rRNAs) are the most abundant cellular RNAs, and their synthesis from rDNA repeats by RNA polymerase I accounts for the bulk of all transcription. Despite substantial variation in rRNA transcription rates across cell types, little is known about cell-type-specific factors that bind rDNA and regulate rRNA transcription to meet tissue-specific needs. Using hematopoiesis as a model system, we mapped about 2,200 ChIP-seq datasets for 250 transcription factors (TFs) and chromatin proteins to human and mouse rDNA and identified robust binding of multiple TF families to canonical TF motifs on rDNA. Using a 47S-FISH-Flow assay developed for nascent rRNA …

Radiation Exposure Determination In A Secure, Cloud-Based Online Environment, Ben C. Shirley, Eliseos J. Mucaki, Peter Rogan

Biochemistry Publications

Rapid sample processing and interpretation of estimated exposures will be critical for triaging exposed individuals after a major radiation incident. The dicentric chromosome (DC) assay assesses absorbed radiation using metaphase cells from blood. The Automated Dicentric Chromosome Identifier and Dose Estimator System (ADCI) identifies DCs and determines radiation doses. This study aimed to broaden accessibility and speed of this system, while protecting data and software integrity. ADCI Online is a secure web-streaming platform accessible worldwide from local servers. Cloud-based systems containing data and software are separated until they are linked for radiation exposure estimation. Dose estimates are identical to ADCI …

Activity Of The Lactate Dehydrogenase Inhibitor Oxamic Acid Against The Fermentative Bacterium Streptococcus Mitis/Oralis: Bactericidal Effects And Prevention Of Daptomycin Resistance In Vitro And In An Ex Vivo Model, Razieh Kebriaei, Arnold S. Bayer, Christian K. Lapitan, Michael J. Rybak, Greg A. Somerville, Nagendra N. Mishra

School of Veterinary and Biomedical Sciences: Faculty Publications

Streptococcus mitis/oralis is a fermentative bacterium that relies on lactate dehydrogenase to balance its redox poise and keep glycolysis active. Metabolomic analysis of an in vitro– derived daptomycin-resistant (DAP-R) S. mitis/oralis strain (351-D10) revealed differences in glucose catabolism relative to its DAP-susceptible (DAP-S) parental strain, 351. Metabolic changes associated with the transition to this DAP-R phenotype suggested that inhibiting glycolysis could alter DAP susceptibility. In addition, the strong reliance of S. mitis/oralis on glycolysis for energy and biosynthetic intermediates suggested that inhibiting glycolysis would adversely affect growth and biomass accumulation. To test these hypotheses, we used the lactate dehydrogenase inhibitor …

Ngly1 Deficiency Affects Glycosaminoglycan Biosynthesis And Wnt Signaling Pathway In Mice, Amy Batten

PANDION: The Osprey Journal of Research and Ideas

Individuals affected by NGLY1 Deficiency cannot properly deglycosylate and recycle certain proteins. Even though less than 100 people worldwide have been diagnosed with this rare autosomal recessive condition, thousands are affected by similar glycosylation disorders. Common phenotypic manifestations of NGLY1 Deficiency include severe neural and intellectual delay, impaired muscle and liver function, and seizures that may become intractable. Very little is currently known about the various mechanisms through which NGLY1 deficiency affects the body and this has led to a lack of viable treatment options for those afflicted. This experiment uses a loss-of-function (LOF) mouse model of NGLY1 Deficiency homologous …

3,6-Dimethoxyxanthone From 2,2’,4,4’- Tetrahydroxy-Benzophenone Via Microwave-Assisted Annulation, Sarah E. Knisely, Faith R. Rosario, Salem F. Gebeyehu, Paige E. Heiple, Robert E. Lee Sr

Journal of the South Carolina Academy of Science

Xanthones are tricyclic aromatic compounds that have multiple pharmacological uses due to their anti-tumor, antioxidant, anti-inflammatory, anti-bacterial, and potentially chemopreventive properties. The target of this research was to optimize a two-step synthesis of 3,6-dimethoxyxanthone (3) from 2,2’,4,4’-tetrahydroxy-benzophenone (1) via microwave-assisted (200 °C, 30-40 min., 150 W) sodium acetate-catalyzed annulation. The product, 3,6-dihydroxyxanthone (2), was then methylated to (3) using dimethyl sulfate (DMS) and sodium carbonate in acetone at reflux. The product yields were 93% (>99% purity) for (2) and 94% (>99% purity) for (3). Characterization was accomplished using ¹H NMR, FTIR, melting point, TLC, HPLC, and GCMS. …