• Design and Synthesis of Novel NSAID Hybrid Conjugates as Potential Anti-inflammatory

      Honkanadavar, Hitesh; Department of Chemistry and Physics (Augusta University, 2019-05)
      Non-steroidal anti-inflammatory drugs are one of the most common drugs administered worldwide as highly effective analgesic, antipyretic and anti-inflammatory agents. The drugs function by inhibiting the COX-2 enzyme system which leads to a decrease in inflammation; however, the drugs also inhibit the COX-1 enzyme system which is critical to maintaining the integrity of the stomach lining as well as proper kidney function. Inhibition of this enzyme system can lead to stomach ulcers and kidney dysfunction. Hybrid conjugates of existing non-steroidal anti-inflammatory drugs (NSAIDs) have already been synthesized with ibuprofen, acetaminophen, and amino acids to increase potency and decrease toxicity. Computational chemistry studies of these compounds show that the free phenol moiety in acetaminophen plays a greater role in the inhibition of the COX-2 enzyme system than the amine moiety. The previous compounds utilized the phenol moiety to form the product. New hybrid conjugates of ibuprofen and acetaminophen via amino acid linkers have been synthesized, leaving the phenol moiety free. The compounds have been characterized by nuclear magnetic resonance and infrared spectroscopy. Biological studies indicate that some of the synthesized compounds are showing improved potency when compared to ibuprofen alone as well as decreased ulcer formation.
    • Characterization of 5HT1B and 5HT7 using Bioluminescence Resonance Energy Transfer

      Adams, Elizabeth; Department of Chemistry and Physics (Augusta University, 2019-05)

      Littlefield, William E; Wade, Margaret; Makkanal, Tina; College of Science and Mathematics; Department of Chemistry and Physics; Panda, Silva; Augusta University (2019-02-13)
      Infectious diseases caused by pathogenic microorganisms are major challenges despite all the steps taken to control or cure. New drug development with high efficacy/selectivity for infectious diseases is a point of interest for many researchers. It has reported that tuberculosis is one of the ten major causes of death in the world. Multi-drug resistance (MDR) is another major concern in bacterial and fungal infections. The present study deals with the development of new conjugates of pyrazinoic acid and isoniazid linked via an amino acid. The synthesized conjugates show promising and interesting results against a variety of microbial strains, tuberculous and non-tuberculous mycobacteria. Molecular modeling studies were used for understanding and validation of the experimental data.

      Farooq, Maheen; Department of Chemistry and Physics; Department of Pharmacology & Toxicology; Spencer, Angela; Lambert, Nevin; Okashah, Najeah; Augusta University (2019-02-13)
      GPCRs are receptors that act in signal transduction pathways via guanosine nucleotide-binding proteins (G proteins). Extracellular ligands act on GPCRs resulting in activation of one or more G protein subtypes (Gs, Gi/o, Gq/11 and G12/13) affecting the concentration of intracellular second messenger molecules ultimately altering cellular function. Cellular responses to external signals are typically studied indirectly by measuring concentration changes in second messengers. However, this approach can be problematic as many GPCRs can activate multiple G protein subtypes, and many second messenger pathways engage in crosstalk. To address this issue, we used Bioluminescence Resonance Energy Transfer (BRET) to directly measure coupling between 5-hydroxytryptamine (5-HT; serotonin) receptors and different G protein family subtypes. We co-transfected cells with plasmid DNA encoding the 5-HT2B or 5-HT4 receptors fused to the bioluminescent protein nanoluciferase (NLuc) as well as plasmid DNA containing G protein subtypes fused to the fluorescent protein Venus. In BRET assays, we found that mGsq couples to 5-HT2B and mGscouples with 5-HT4 in response to 5-HT activation. These results are consistent with the literature. Interestingly, initial studies suggest that activated 5-HT4 shows secondary coupling to mGsi highlighting the potential novel signaling pathways that can be elucidated using this technique.

      Honkanadavar, Hitesh H; Tran, Queen; Department of Chemistry and Physics; Panda, Silva; Augusta University (2019-02-13)
      Quinolones are one of the most important synthetic antibacterial agents have been widely used in the treatment of diverse infections including urinary tract, respiratory and bone joint as well as sexually transmitted diseases, prostatitis, pneumonia, and acute bronchitis. However, quinolone resistance increases towards many Gram-negative and Gram-positive species. Molecular conjugation has been known for the rational design of new biologically active entities by fusion of compounds and/or pharmacophores recognized and derived from known bio-active molecules. The present study directs towards the construction of novel quinolone-triazole conjugates and investigation of their antimicrobial properties. The detail results will be discussed at the conference.

      Nelson, Brenda; College of Science and Mathematics; College of Nursing; Langley-Brady, Dawn; Augusta University (2019-02-13)
      Dysmenorrhea effects 20% of women causing missed school and work days and interferes with daily life. Dysmenorrhea is caused by menstrual uterine contractions which may result in pain, nausea, vomiting and headaches. Many women utilize pharmacological symptom management, but experience side effects such as edema, libido reduction and increased symptom severity. Aromatherapy is a holistic non-pharmacological approach to symptom reduction. Aromatherapy is the use of essential oils via inhalation or topical application to relieve pain, stress and more.� The purpose of this project is to review the literature surrounding�Lavandula angustifolia�(lavender) and dysmenorrhea to give a foundation for future research. PubMed, TRIP, and Cochrane Library databases were searched for peer-reviewed journals articles in English and published within the last 10 years with the following keywords: dysmenorrhea, lavender, aromatherapy and human. The literature review resulted in six articles meeting inclusion criteria. These articles established the effectiveness of lavender in reducing dysmenorrhea pain in the first three days of menstruation, through inhalation and abdominal application. Lavender essential oil is also effective in reducing nausea and headaches resulting in an alternative for women experiencing dysmenorrhea. Aromatherapy has fewer risks than pharmacological and surgical approaches to dysmenorrhea management and should be studied further.

      Weathers, Angel; Department of Chemistry and Physics; Lebedyeva, Iryna; Augusta University (2019-02-13)
      �Click� Chemistry is a convenient technique often applied during the synthesis of various bioconjugates. Several methods have been developed to administer �click� chemistry. Copper(1)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions usually provide high chemoselectivity under green reaction conditions, and good to great yields. Because of this, CuAAC reactions serve many applications in chemical biology. In copper halide catalyzed reactions copper iodide is frequently used to facilitate transformational changes within the reaction. Copper(1) is combined with salts, metal complexes, or ionic liquids to provide effective catalytic systems for reactions. The use of co-solvent systems such as the one used in this research project, dimethylformamide and water, improves reaction efficiency. The alkyne moiety is an indispensible component of �click� chemistry reactions. Coumarins are the specific class of fluorophores examined in this research project because they are highly sensitive fluorescent laser dyes that have extended spectra range, high emission quantum yields, and better solubility compared to more complex fluorescent tags. Amino acids are often used as building blocks because they are recognized by cell membrane proteins more readily. In this project, a number of amino acids labeled with coumarin tags through CuAAC catalyzed 1,2,3-triazole links have been developed to study their fluorescent properties.

      Patel, Chandani; Patel, Reeya; College of Science and Mathematics; Department of Orthopedic Surgery; Fulzele, Sadanand; Augusta University (2019-02-13)
      MicroRNAs (miRNAs) have been known to play a key role in bone regulation. Some miRNAs have been observed to increase bone formation via osteoblast formation and others seem to be involved in bone resorption via osteoclast formation. In this study, we aim to observe which miRNA of those secreted by cells during a traumatic brain injury (TBI) are involved in bone formation or bone resorption. Our focus miRNAs were: miRNA-151, miRNA-6991, miRNA-27a, miRNA-92, and miRNA-1224. Using mouse bone marrow monocytes (BMCs), we have induced osteoclast formation by feeding media containing macrophage colony stimulating factor (M-CSF) as well as receptor activator of nuclear factor kappa-B ligand (RANK-L). After osteoclastogenesis, it has been observed via tartrate resistant acid phosphatase (TRAP) staining that miRNA-151 and miRNA-6991 have been up-regulated during osteoclast differentiation. Of the ones examined in our study, miRNA-27a, miRNA-92, and miRNA-1224 have shown an increase during osteoblast differentiation. The observations from this study can contribute insight for creating possible therapeutic methods for osteoporosis related diseases.

      Hammond, Caroline; Wyman, Kailey; Blair, Gregory; Department of Chemistry and Physics; Agee, Brian; Augusta University (2019-02-13)
      Since the 1990�s, scientists have been attempting to make chemical synthesis procedures more environmentally friendly.� One area of environmental concern is the amount of electricity required to provide enough energy to complete an experiment. Recently proposed solar reflectors developed from satellite dishes have the ability to be incorporated into student laboratory procedures to eliminate electricity use while demonstrating green chemistry techniques at the same time. As a result, demand to incorporate more green chemistry techniques into student laboratories has increased. An effective means for minimizing the amount of electricity needed to drive chemical reactions to completion is proposed through the use of solar parabolic reflectors. A comparative study was conducted using an electrical and solar heat source on the Williamson Ether synthesis of 2-butoxynaphthalene. This reaction was chosen as the test reaction due to its widespread use among many undergraduate chemistry programs.
    • Investigating the Interaction Between G Proteins and the 5-HT1E and 5-HT2C Serotonin Receptors Using BRET

      Little, Lauren; Department of Biological Sciences; Department of Chemistry & Physics; Spencer, Angela; Augusta University (2019-02-13)
      G protein-coupled receptors (GPCRs) are important mediators in cellular signaling and are common targets of drug action. GPCRs are responsible for the transduction of extracellular signals into intracellular signals, mediated by G proteins of four types: Gs, Gi, Gq, and G12/13. A thorough understanding of a signaling pathway involves determining which G protein is coupled to a signal-activated GPCR. In this project, a technique called Bioluminescence Resonance Energy Transfer (BRET) was used to measure the interaction between an activated GPCR from the serotonin (or hydroxytryptamine, 5-HT) receptor family, and G proteins from each subtype. The cDNA for serotonin receptors 5-HT1E�and 5-HT2C�was fused with the gene for a luminescent protein called Nanoluciferase (Nluc). Then, the receptor-Nluc DNA along with DNA containing a G protein tagged with a fluorescent protein (Venus) was transfected into mammalian cells for expression. Data from BRET assays suggest that the 5-HT1Ereceptor couples to the Go and Gi subclasses of G proteins upon serotonin activation while the 5-HT2C�receptor couples to the Gq class of G proteins. Profiling serotonin receptors will deepen our understanding of serotonin receptors, associated diseases, and the drugs that target them.
    • Design, Synthesis, and Anti-inflammatory Studies of NSAID Hybrid Conjugates

      Honkanadavar, Hitesh; Department of Chemistry & Physics; Panda, Siva; Augusta University (2019-02-13)
      Non-steroidal anti-inflammatory drugs are one of the most common drugs administered worldwide as highly effective analgesic, antipyretic and anti-inflammatory agents. The drugs function by inhibiting the COX-2 enzyme system which leads to a decrease in inflammation; however, the drugs also inhibit the COX-1 enzyme system which is critical to normal renal function, gastric mucosal integrity, vascular homeostasis, and the autocrine response to circulating hormones which can lead to gastric ulcers and renal dysfunction. Hybrid conjugates of existing non-steroidal anti-inflammatory drugs (NSAIDs) have already been synthesized with Ibuprofen, Acetaminophen, and amino acids to increase potency and decrease toxicity. Computational chemistry studies of these compounds show that the free phenol moiety in acetaminophen plays a greater role in the inhibition of the COX 2 enzyme system than the amine moiety. The previous compounds utilized the phenol moiety to form the product. New hybrid conjugates of Ibuprofen and Acetaminophen via amino acid linkers have been synthesized, leaving the phenol moiety free. The compounds have been characterized by NMR and IR. Biological studies indicate that some of the synthesized compounds are showing improved potency when compared to Ibuprofen alone. Computational chemistry studies and molecular modeling will be used to support the�in-vivo�biological activity.
    • The Study of 5ht-1d and 5ht-1f Receptor Interactions with Mini G Proteins via Bret Analysis

      Trang, Amy; Department of Chemistry & Physics; Department of Pharmacology and Toxicology; Spencer, Angela; Lambert, Nevin; Augusta University (2019-02-13)
      G protein-coupled receptors (GPCRs) are receptors involved in signal transduction, a process for converting extracellular signals into internal messages to elicit a cellular response. Signal transduction pathways involve activating various G protein subtypes (Gs, Gi/o, Gq/11�and G12/13) which typically lead to second messenger production. Traditionally, second messenger concentration assays are used to identify GPCR coupling with G protein(s), but they are not efficient in profiling GPCRs since they compare the concentrations from different downstream signals. Instead, novel tools, such as Bioluminescence Resonance Energy Transfer (BRET) and mini G (mG) proteins, can be used to profile GPCRs. BRET is a technique that provides quantitative data when protein-protein interaction occurs and requires the proteins of interest to be fused with either a bioluminescent protein or fluorescent protein. In this study, we used mG proteins representing each G protein subtype to identify 5-hydroxytryptamine (5-HT; serotonin) receptor coupling upon serotonin stimulation. Through BRET assays, we determined that both the 5-HT1D�and 5-HT1F�receptors couple primarily with the mGsiand mGo�classes of mG proteins. This supports previous studies that these receptors couple to Gi/o�proteins and suggests that the use of mG proteins in BRET assays is an effective tool for GPCR profiling.
    • Unconventional Coupling of 5HT7 receptors to Gs heterotrimers

      Adams, Elizabeth; Department of Pharmacology and Toxicology; Lambert, Nevin; Augusta University (2019-02-13)
      GPCRs play a major role in cell signaling through their interactions with heterotrimeric G proteins. In conventional models of GPCR-G protein coupling, agonist binding promotes a conformational change within the receptor, which then associates with G proteins, facilitating the exchange of GDP for GTP. GTP-bound G proteins dissociate from the receptor and exert their effects on downstream signaling molecules. Previous studies suggest that serotonin 5HT7 receptors associate with Gs�heterotrimers prior to agonist binding, and that 5HT7-Gs�complexes dissociate after the G protein is activated. Here we study this unconventional mode of coupling using bioluminescence resonance energy transfer (BRET) between luciferase-tagged 5HT7 receptors and Gs�heterotrimers labeled with Venus. Our results confirm that 5HT7 receptors interact with inactive (GDP-bound) Gs�heterotrimers in the absence of an agonist, and that this interaction is stabilized by the inverse agonist methiothepin. Stimulation with the endogenous agonist serotonin (5HT) decreased BRET between 5HT7 receptors and Gs, indicating that the activation of the receptor leads to 5HT7-Gscomplex dissociation. Interestingly, Gs�activation was not required for complex dissociation. These results are consistent with the hypothesis that 5HT7 receptors couple to Gs�heterotrimers via an unconventional mechanism involving ligand-sensitive complexes of receptors and inactive Gs.
    • Exploring the minimum flow rate limit in electro co-flow

      Overlie, Benjamin; Department of Biological Sciences; Department of Chemistry & Physics; Millan, Josefa Guerrero; Augusta University (2019-02-13)
      Controlled generation of micron and sub-micron sized drops continues to be of strong interest for the scientific community due to the variety of applications in fields like cosmetics, food industry, and drug delivery among others. By flowing two immiscible liquids into a glass-based microfluidic device, we can make emulsion drops with a minimum size of the order of the tip size. Adding an external electric field, similarly to what it is done in the classical electrospray, allows the generation of droplets with sizes below the smallest geometrical characteristic of the device. In this work, we are focused on the region of small flow rates. There is a minimum flow rate below which a cone-jet cannot be formed regardless of the applied voltage. This limit marks the minimum drop size that could be generated. We study pairs of liquids with different viscosities and conductivities using high speed microscopy and current measurements. With these data we will try to understand this limit and the characteristics of the modes observed in this region.
    • Exact diagonalization RIXS studies of the doped 1d t1-t2-J model at the O K-edge

      Price, Gregory; Department of Chemistry & Physics; Datta, Trinanjan; Augusta University (2019-02-13)
      Resonant inelastic x-ray scattering (RIXS) is a novel spectroscopic method for probing charge and spin excitations in quantum magnets. In one dimension, where quantum fluctuations are most prominent, a system of interacting electrons can support fractionalized spinless charge excitations (holons) and chargeless spin excitation (spinons). Currently, X-ray spectroscopic techniques such as RIXS can excite the O K-edge core electrons of correlated quantum magnets to probe the physical nature of the above mentioned spin-charge separated state. Using exact diagonalization we investigate the O K-edge RIXS response of the one dimensional antiferromagnetic spin chain compound with nearest and next-nearest neighbor hoppings. We also study the spin-anisotropic version of the same model. Interaction of the core electrons with the X-rays generate multi-spinon excitations in the RIXS spectrum, for example in strontium copper oxide. We find that the RIXS spectrum of the t1-t2-J model with spin anisotropy presents a rich source of physical information, including allowing us to identify microscopic pathways for how the quantum spin fluctuations control the appearance of the four spinon excitations observed in the isotropic O K-edge spectrum.
    • Concentrations of Iron, Copper, Nickel, and Zinc in Rae's Creek

      Bridgers, Aerial; Department of Chemistry & Physics; Klug, Christopher; Augusta University (2019-02-13)
      Heavy metals can enter water systems through a variety of methods, such as through soil run-off, rain, or industrial activity near the system. Many of these heavy metals are toxic to both the wildlife and people around the system if present in high enough concentrations. The aim of this research was to create a model for a local water system, Rae's Creek, outlining the concentrations of iron, copper, nickel, and zinc present throughout a seven-month period. Additionally, this research sought to pinpoint any correlation between increases in metal concentrations and outside events, such as rain or the Master's Tournament held yearly in Augusta. Results indicated that copper and zinc concentrations were well above guidelines set for recreational water quality by the Environmental Protection Agency, while iron and nickel concentrations were generally below the limitations set for their concentrations. While rain had no observed effect on the heavy metal concentrations, there are two specific dates where all four metals had a marked increase in concentration. However, it is inconclusive as to what caused this increase.
    • Transport properties in Graphene Bilayer

      Trowel, Alonte; Department of Chemistry & Physics; Datta, Trinanjan; Augusta University (2019-02-13)
      Graphene is a single layer of carbon atoms arranged in a hexagonal pattern. It has many potential technological applications and provides a testbed to verify fundamental concepts in physics. Using quantum mechanical transmission and reflection amplitudes we study the transport properties of bilayer graphene. For the parameter range that We explored we find that the transmission probability is controlled by the applied bias. We also outline how this approach can be utilized to study oligomers and oligoacenes.
    • Design and Manufacture of Low-Cost Real-Time Feedback CPR Manikin

      Sangari, Anish; Sood, Nitish; Department of Chemistry & Physics; Augusta University (2019-02-13)
      Cardiopulmonary Resuscitation (CPR) is a life-saving technique used when a person stops breathing or a heart stops beating. Immediate CPR can double or triple survival rates after cardiac arrest. While many CPR training courses use non-electronic CPR manikins, recent literature has shown that training on a real-time feedback CPR manikin improves functional outcomes such as chest compression rate and mean tidal volume. However, current commercially available real-time feedback manikins either only measure metrics on chest compressions or are available at very high prices, making training a class on such manikins infeasible. Accordingly, we have designed, constructed, and tested a low-cost Arduino microcontroller-based CPR manikin that provides real-time feedback to trainees on critical metrics including force of compressions, rate of compressions, hands-off time, percentage of full chest recoils, angle of neck tilt, and other steps in ventilations. Visual and auditory feedback on these metrics is delivered to trainees, allowing them to adjust their performance in real time. Additionally, data from each training session is saved and assigned to a user profile, so that multiple trainees can review their progress throughout their training. Future research will be conducted on the efficacy of training on this manikin compared to commercially available manikins.
    • Iron, Copper, Nickel, and Zink Ion Concentrations in Rae's Creek

      Bridgers, Aerial; Department of Chemistry and Physics (Augusta University, 2018-12)