Chemistry Commons^™

Fragment-Based Drug Discovery Of Sars-Cov-2 Therapeutics, Hannah Johnson '22

Student Publications & Research

During the COVID-19 pandemic, the usual drug development timeline has been substantially condensed. This shortened timeline aims to allow for a safe and effective therapy to be discovered as soon as possible as the number of global COVID cases rise. Moreover, the COVID Moonshot open-sourced initiative has allowed the development of a COVID antiviral to accelerate. After the published fragment screening on the main protease (MPro) of SARS-CoV2 yielded 66 fragment hits, a fragment (x0434) was selected to build novel compounds. SeeSAR was used to gather preliminary knowledge of the three-dimensional structure of the biomolecular targeted protein and selected fragment …

Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = …

Colloidal Nanomaterial Surface Chemistry And Characterization Studied By Linear And Nonlinear Spectroscopy, Asela Sampath Dikkumbura

LSU Doctoral Dissertations

Recent studies have demonstrated the use of nanomaterials such as metallic nanoparticles, liposomes, and polymer microparticles for biomedical applications, encompassing the field of nanomedicine. For developing novel core-shell metallic nanoparticles with controlled surface morphology, the in situ growth dynamics of colloidal silver-gold core-shell (Ag@Au CS) nanoparticles (NPs) in water are monitored in a stepwise synthesis approach using time-dependent second harmonic generation (SHG) and extinction spectroscopy. Transmission electron microscopy images show that the CS NP surface morphology becomes more smooth and uniform as the reaction proceeds, corresponding to lower, stable SHG signals and narrower plasmonic spectra that are compared to finite-difference …

Synergistic Anticancer Response Of Curcumin And Piperine Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against Glioblastoma Multiforme, Xinyi Zhao, Bilal Javad, Daxing Cui, James Curtin, Furong Tian

Articles

Glioblastoma multiforme (GBM) is the most aggressive and commonly diag- 11 nosed brain cancer and presents a strong resistance to routine chemotherapeutic drugs. 12 The present study involves the synthesis of Lignin-g- p (NIPAM-co-DMAEMA) gold 13 nanogel, loaded with curcumin and piperine to treat GBM. The application has three 14 functions: (1) overcome the limitations of biodistribution, (2) enhance the toxicity of an- 15 ticancer drugs against GBM, (3) identify the uptake pathway. Atom transfer radical 16 polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with 17 the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and …

Cyclic Peptide-Gadolinium Nanocomplexes As Sirna Delivery Tools, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Dindyal Mandal, David Stickley, Stephanie Nagasawa, Joshua Long, Sandeep Lohan, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)₅C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)₅C]-GdNPs, in the range of 240 to 260 nm upon mixing with an aqueous solution of GdCl₃. Herein, we report [(WR)₅C]-GdNPs as an efficient siRNA delivery system. The peptide-based gadolinium nanoparticles (50 µM) did not exhibit significant cytotoxicity (~93% cell viability at 50 µM) in human leukemia T lymphoblast cells (CCRF-CEM) and triple-negative breast cancer cells (MDA-MB-231) after 48 h. Fluorescence-activated cell sorting (FACS) analysis indicated …

Reinvigorating A Technical Countering Weapons Of Mass Destruction Distance Learning Graduate Certificate Program, James C. Petrosky, Gaiven Varshney, Jeremy Slagley, Sara Shaghaghi

Faculty Publications

Current Countering Weapons of Mass Destruction (CWMD) demands can be divided broadly into policy and science. The science of chemical, biological, and radiological/nuclear weapons informs the limits of development, production, employment, operation, detection, risk characterization, human and material protection, and medical intervention. In short, the science of weapons of mass destruction (WMD) should precede and inform the development of policy. It is to this end that the Air Force Institute of Technology (AFIT) CWMD program was re-established, providing a technical educational option for practitioners to understand the science behind a very technically challenging subject.

Atomistic Simulations And In Silico Mutational Profiling Of Protein Stability And Binding In The Sars-Cov-2 Spike Protein Complexes With Nanobodies: Molecular Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structure-functional studies have recently revealed a spectrum of diverse high-affinity nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we combine atomistic simulations with the ensemble-based mutational profiling of binding for the SARS-CoV-2 S-RBD complexes with a wide range of nanobodies to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations. Using an in silico mutational profiling approach for probing the protein stability and binding, we examine dynamics and energetics of the SARS-CoV-2 complexes with single nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E + …

Metal-Free Domino Amination-Knoevenagel Condensation Approach To Access New Coumarins As Potent Nanomolar Inhibitors Of Vegfr-2 And Egfr, Essam M. Eliwa, Marcel Frese, Ahmed H. Halawa, Maha M. Soltan, Larissa V. Ponomareva, Jon S. Thorson, Khaled A. Shaaban, Mohamed Shaaban, Ahmed M. El-Agrody, Norbert Sewald

Center for Pharmaceutical Research and Innovation Faculty Publications

A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach to construct new coumarin analogous (4a-f and 8a-e) was described. Further, new formyl (5a,d-f) and nitro (9a,d-f) coumarin derivatives were synthesized via C-N coupling reaction of various cyclic secondary amines and 4-chloro-3-(formyl-/nitro)coumarins (1a,c), respectively. The confirmed compounds were screened for their in vitro anti-proliferative activity against KB-3-1, A549 and PC3 human cancer cell lines using resazurin cellular-based assay. Among them, coumarin derivatives 4e and 8e displayed the best anti-cervical cancer potency (KB-3-1) with IC₅₀ values of 15.5 ± 3.54 …

Neuron-Derived Extracellular Vesicles Modulate Microglia Activation And Function, Hui Peng, Brock T. Harvey, Christopher I. Richards, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Microglia act as the immune cells of the central nervous system (CNS). They play an important role in maintaining brain homeostasis but also in mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for neuroimmune regulation and subsequent effects on CNS integrity. However, the molecular mechanisms of neuron-glia communication in regulating microglia function are not fully understood. One recently described means of this intercellular communication is via nano-sized extracellular vesicles (EVs) that transfer a large diversity of molecules between neurons and microglia, such as proteins, lipids, and nucleic acids. To determine the effects of …

Enhanced Platinum (Ii) Drug Delivery For Anti-Cancer Therapy, Marek T. Wlodarczyk

Dissertations, Theses, and Capstone Projects

Over the years, anti-cancer therapies have improved the overall survival rate of patients. Nevertheless, the traditional free drug therapies still suffer from side effects and systemic toxicity, resulting in low drug dosages in the clinic. This often leads to suboptimal drug concentrations reaching cancer cells, contributing to treatment failure and drug resistance. Among available anti-cancer therapies, metallodrugs are of great interest. Platinum (II)-based agents are highly potent and are used to treat many cancers, including ovarian cancer (OC). Cisplatin (cis-diaminedichloroplatinum (II)) is the first Food and Drug Administration (FDA)-approved metallodrug for treatment of solid tumors, and its mechanism …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Unintended Consequences Of Air Cleaning Chemistry, Douglas B. Collins, Delphine K. Farmer

Faculty Journal Articles

Amplified interest in maintaining clean indoor air associated with the airborne transmission risks of SARS-CoV-2 have led to an expansion in the market for commercially available air cleaning systems. While the optimal way to mitigate indoor air pollutants or contaminants is to control (remove) the source, air cleaners are a tool for use when absolute source control is not possible. Interventions for indoor air quality management include physical removal of pollutants through ventilation or collection on filters and sorbent materials, along with chemically reactive processes that transform pollutants or seek to deactivate biological entities. This perspective intends to highlight the …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

2021 Scas Annual Meeting Program And Bulletin

Journal of the South Carolina Academy of Science

No abstract provided.

The Effect Of Poverty Levels And Minority Percentages On Lead Content In South Carolina Midlands School Drinking Water, Kathleen L. Barfield

Journal of the South Carolina Academy of Science

No abstract provided.

Thermal Properties Of 18f-Fdg Uptake And Imaging In Positron Emission Tomography Scans Of Cancerous Cells, Carleigh R. Eagle

PANDION: The Osprey Journal of Research and Ideas

Positron Emission Tomography (PET) scans can utilize a radioactive tracer, in this case 2-deoxy2-[fluorine-18] fluoro-D-glucose (¹⁸F-FDG), to visualize malignant tumors in cancer patients. The uptake was compared to glucose to understand the difference in thermal properties, which contribute to the ability to image the cancerous cells. The uptake of ¹⁸F-FDG by cancer cells and the imaging process of positron emission tomography were reviewed from a thermodynamic perspective. Gastrointestinal and neurological imaging techniques were reviewed to understand the role of PET imaging in different areas of the human body.

Correlation Effects On Intramolecular C-H...Oh And O-H...O Hydrogen Bond Interactions In Azelaic Acid: An Ab Initio Study, Sabina Kalata, Alina Huang, Ruben Parra

DePaul Discoveries

Electron correlation effects on both conventional, O-H…O, and nonconventional, C-H…O, intramolecular hydrogen bonds present in a selected azelaic acid folded conformation were evaluated ab initio using HF and MP2 methodologies. The relative strength of the hydrogen bonds was examined through different indicators derived from geometry, vibrational frequencies, and electron density along the hydrogen bond path. The HF method results in weaker O-H…O and C-H…O hydrogen bonds when compared with the corresponding results using the MP2 method. Additionally, the stability of the folded azelaic conformation is found to depend on the level of theory used. Accordingly, the zero-point corrected energies of …

Quantifying Phosphatidylethanol From Blood Samples, James V. Defrancesco, Majid Afshar

Chemistry: Faculty Publications and Other Works

Disclosed herein is a method for quantifying phosphatidylethanol (“ PEth ”), direct ethanol biomarker, from a blood sample using gas chromatography mass spectrometry. The method disclosed herein is useful for diagnosing acute and chronic alcohol abuse.

Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton

Graduate Theses/Dissertations

Diethylene glycol monoethyl ether (DEGEE) is a promising solvent component in topical cream formulations due to its superior solubilizing abilities with certain active pharmaceutical ingredients. One of the goals of this study is to characterize the effects of pH on the physical and chemical stabilities of topical cream formulations containing particularly high concentrations of DEGEE by characterizing a full topical pH profile of 3.5 – 9.0. The second goal is to evaluate the presence, amount, and characteristics of lyotropic liquid crystals (LLCs), molecularly structured in a lamellar phase, in a model cream emulsion utilizing polarized light microscopy (PLM). The presence …

Ganglioside Alters Phospholipase Trafficking, Inhibits Nf-Κb Assembly, And Protects Tight Junction Integrity, John J. Miklavcic, Qun Li, Jordan Skolnick, Alan B. R. Thomson, Vera C. Mazurak, Michael Tom Clandinin

Food Science Faculty Articles and Research

Background and Aims: Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. The objective of this study was to examine mechanisms by which dietary gangliosides exert beneficial effects on intestinal health.

Methods: Studies were conducted in vitro using CaCo-2 intestinal epithelial cells. Gangliosides were extracted from milk powder and incubated with differentiated CaCo-2 cells after exposure to pro-inflammatory stimuli. …

Soft Lithographic Replication Of High Length-Scale Micropillars From Laser-Ablated Fused-Silica Templates, Jason Pitts

University Honors Theses

Soft lithography is a well-established route to wafer-scale reproduction of micro- and nanoscale features in a wide variety of materials. Nevertheless, micron length scales have yet to be explored, despite the potential utility of such structures. Here, polymer micropillars of 6-12 μm length, approximately 0.5-1.5 μm wide at 10 μm spacing are reproduced from a polydimethylsiloxane (PDMS) mold made from patterned cellulose acetate (CA). The patterned CA was cast from a rigid fused silica template machined by a pulsed femtosecond laser. Pore topographic features were successfully reproduced in Norland Optical Adhesive (NOA), polycaprolactone (PCL), Nafion, acrylonitrile butadiene styrene (ABS), and …

Repurposing Drugs To Treat Heart And Brain Illness, Maranda S. Cantrell, Alejandro Soto-Avellaneda, Jackson D. Wall, Aaron D. Ajeti, Brad E. Morrison, Lisa R. Warner, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

Drug development is a complicated, slow and expensive process with high failure rates. One strategy to mitigate these factors is to recycle existing drugs with viable safety profiles and have gained Food and Drug Administration approval following extensive clinical trials. Cardiovascular and neurodegenerative diseases are difficult to treat, and there exist few effective therapeutics, necessitating the development of new, more efficacious drugs. Recent scientific studies have led to a mechanistic understanding of heart and brain disease progression, which has led researchers to assess myriad drugs for their potential as pharmacological treatments for these ailments. The focus of this review is …

Design, Synthesis And Evaluation Of Molecules With Selective And Poly-Pharmacological Actions At D1r, D3r And Sigma Receptors, Pierpaolo Cordone

Dissertations, Theses, and Capstone Projects

The dopamine D3 receptor (D3R) is one of the most studied receptors involved in drug addiction. One of the most common strategies to treat substance use disorders is via D3R antagonism. The majority of the D3R antagonists synthesized so far have poor pharmacokinetic properties and/or lack selectivity toward D3R. In this thesis, the design, synthesis and biological evaluation of novel molecules that target the dopamine D1 receptor (D1R), D3R and the serendipitous discovery of molecules that target s receptors will be described.

Chapter 1 presents a survey of the fundamental pharmacology of D1R, D3R and s receptors and the therapeutic …

Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah

Seton Hall University Dissertations and Theses (ETDs)

Abstract

The emerging field of RNA nanotechnology has led to rapid advances in the applications of RNA in chemical biology, medicinal chemistry, and biotechnology. At the forefront of its utility is the ability to self-assemble multiple siRNAs into nanostructure formulations capable of targeting selected oncogenes and potentiating the gene therapy of malignant tumors. Self-assembled siRNA integrates multiple siRNAs within a single molecular platform for silencing multiple oncogenic mRNA targets with high precision and efficacy to potentially induce cancer cell apoptosis through the RNA interference (RNAi) pathway. Furthermore, the conjugation of siRNA self-assemblies with bio-active probes results in multi-functional theranostic (therapy+diagnostic) …

Advancing The Preclinical Development Of Secondary Metabolites From Cacospongia Mycofijiensis For The Treatment Of Cancer, Joseph Morris

Natural Sciences and Mathematics | Biological Sciences Master's Theses

The marine sponge Cacospongia mycofijiensis from the Indo-Pacific has proven to be a source of structurally diverse secondary metabolites that are biologically active against a variety of distinct targets. Current interest in the secondary metabolites of C. mycofijiensis largely stems from a) their potent and preferential cytotoxicity for cancer cell lines versus normal cells, making many of them promising leads as cancer therapeutics and b) the novel mechanisms of action responsible for their impressive cytotoxicity. However, limited compound availability has resulted in a paucity of studies aimed at advancing the preclinical development of these secondary metabolites from C. mycofijiensis for …

Reeling In New Antibiotics: Synthesis And Antimicrobial Susceptibility Testing Of Zinc-Binding Clavanins From Styela Clava (Sea Squirt), Eduardo Badillo-Colberg

Honors Scholar Theses

Clavanins have been a quite rarely studied antimicrobial peptide (AMP) family. Though the data in the few studies published on the matter and in theoretical experimental data presented by the Wang lab in their peptide library creation [14], in that the members of this family could potentially be quite effective novel antimicrobial candidates. Among those that have been targets of studies, Clavanin A has been at the forefront of this endeavor of finding effective novel antimicrobial peptides[14]. In these aforementioned studies, Clavanin A has been shown to be quite effective against many different bacterial strains, which begs the question as …

Extreme Weather And Its Impacts On Human Civilizations: An In-Depth Investigation Of Causes And Effects, Jason Zabel

Senior Honors Theses

Extreme weather has impacted humanity since creation and is an important topic that deserves examination. In this thesis, the main event that is presented and analyzed is the extreme haze that clouded much of China’s skies in 2013. Further, the impacts this major event had on people, including changes in population movement, death/injury rate, and changes in atmospheric chemistry due to the high concentration of particulates are discussed. Subsequent examples that will be explored include Hurricane Katrina and the eruption of Mt. St. Helens. The main contention of this thesis is that the effects extreme weather has on human civilization …

Synthesis And Self-Assembly Of Amphiphilic Block Copolymers For The Fabrication Of Non-Spherical Polymersomes, Tamuka Chidanguro

Dissertations

Polymersomes, also known as polymer vesicles, have gained a lot of interest over the past two decades. These hollow spherical systems are made via the self-assembly of amphiphilic block copolymers and have found use in a range of areas from drug delivery, to cellular models, to nanoreactors. Their hollow nature allows them to carry hydrophilic cargo in their inner compartment and hydrophobic cargo in their membrane. Over the last decade, increasing efforts have focused on controlling the morphology of polymersomes. Research has shown that polymersome morphology plays an important role for instance in drug delivery, where tubular or rod-like vesicles …

Developing A Microdialysis Sampling-Based Biofilm/Macrophage Co-Culture Model, Alda Diaz Perez

Graduate Theses and Dissertations

The host immune system and bacterial cells are known to interact during the human lifetime. Bacteria secrete a wide variety of signaling molecules, known as quorum sensing (QSC) molecules, that modulate the host immune system. While immune-biofilm interactions involve this chemical signaling network, the mechanisms through which this occurs are not well understood. This work aimed to develop a new method that can be used not only in vitro settings but also in vivo. The microdialysis sampling technique has widely been used in in vitro and in vivo settings in humans, mice, and rats for the collection of neuropeptides, cytokines, …

Heavy Metals In Ends Liquids: A Comparative Analysis Of Products From The United States, England, Canada, And Australia, Ashleigh Coggins-Block

Forensic Science Theses

The International Tobacco Control (ITC) Policy Evaluation Project 4-Country Survey, which this thesis is a part of, aims to compare policies and electronic nicotine delivery system (ENDS) products between the United States, England, Canada, and Australia. Since they can pose many serious health risks, this thesis investigated the presence of and source of heavy metals, including lead, nickel, chromium, and cadmium, in ENDS e-liquids. The source of these metals in ENDS e-liquids has been disputed between cultivated tobacco used to derive nicotine and the metal parts of ENDS devices. ENDS purchased in 2017 from each of the four countries of …