Pharmacy and Pharmaceutical Sciences Commons^™

Design And Synthesis Of Small Molecular Inhibitors Of Dcn1-Ube2m Interaction, Tucker J. Moseley

Theses and Dissertations--Pharmacy

Over the last century, advancements in medicine have been made to improve cancer patients' outcomes. The discovery of new druggable targets is essential to achieving this goal. Defective in Cullin Neddylation 1 is a proven oncogenetic driver that may lead to better clinical outcomes when targeted. In efforts to further improve a series of novel small molecular inhibitors of the DCN1 and UBE2M protein-protein interaction, the Guy lab has designed and synthesized 26 new compounds. These compounds were designed to specifically target the UBE2M N-Acetyl sub-pocket on DCN1 that was not occupied by compounds previously described in the literature.

New Tools For Biocatalysis: Studies On The Carminomycin 4-O-Methyltransferase Dnrk, Elnaz Jalali

Theses and Dissertations--Pharmacy

Methyltransferases (MTs) are ubiquitous enzymes commonly involved in biosynthesis and regulation. The fundamental goal of this thesis was to explore the permissive nature of methyltransferases and leverage this unique biocatalytic feature to develop a new platform for chemoselective intramolecular cyclization reactions. To realize this ambitious goal, this thesis project set out to probe the substrate specificity of multiple natural product tailoring enzymes (MTs and glycosyltransferases), identify model substrates common to multiple such tailoring enzymes and subsequently establish multi-enzyme tandem reactions that would set the stage for a subsequent chemoselective intramolecular cyclization reaction. Chapter One highlights current state of the art …

Soft X-Ray And Susceptibility Based Magnetic Resonance Imaging To Map Iron Distribution In Apples: Initial Results To Model Iron Storage In Water-Deficient Or Dehydrated Biological Tissue, Subhendra N. Sarkar, Eric Lobel, Evans Lespinasse, Zoya Vinokur, Analia Basilicata, Sonia Orellana, Maria Orellana, Aaliyah Salmon, Joanna Syska, Aravis Mcbroom, Jian Wang, Anam Riaz, Jodi-Ann Douglas

Publications and Research

Radiology departments have contributed significantly to greenhouse gases including release of toxic imaging contrast media to environment. We feel Radiology also has several spectroscopy and imaging tools that may apply to monitor and support cleaner environmental goals. The current manuscript is one of the firsts to prompt Radiology to move in that direction by non invasive imaging of bio metals that are less abundant in biological tissues but play key roles as co-factors in tissue structure and function. Conventional analytical tools are mostly invasive and cannot characterize the native oxidation states of bio metals. We chose carbohydrate matrix of metal-rich …

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Lysosomes, Curcumin, And Anti-Tumor Effects: How Are They Linked?, Qian Shen, Xue Pan, Yi Li, Junchen Li, Chuanlong Zhang, Xiaochen Jiang, Fudong Liu, Bo Pang

Faculty, Staff and Student Publications

Curcumin is a natural active ingredient from traditional Chinese medicine (TCM) that has multi-target characteristics to exert extensive pharmacological activities and thus has been applied in the treatment of various diseases such as cancer, cardiovascular diseases, nervous system, and autoimmune disorders. As an important class of membranous organelles in the intracellular membrane system, lysosomes are involved in biological processes such as programmed cell death, cell metabolism, and immune regulation, thus affecting tumor initiation and progression. It has been shown that curcumin can modulate lysosomal function through the aforementioned pathways, thereby affecting tumor proliferation, invasion, metastasis, drug resistance, and immune function. …

Assessing Drug Development Proporties Of Antithrombotic And Anti - Cancer Agents, Elsamani I. Abdelfadiel

Theses and Dissertations

The current GAG anticoagulants such as heparin, heparin derivatives, and vitamin K antagonists, such as warfarin continue to be the backbone of anticoagulant therapy. These drugs act through an indirect mechanism to convey inhibition of several coagulation enzymes. However, xv their use leads to several serious adverse effects, such as excessive bleeding risk and unpredictability of patient response. Regardless of their clinical achievement, every individual agent is accompanied by several side effects, particularly major/minor bleeding, thrombocytopenia, drug-food or drug-drug interactions, or absence of antidote. Of all these side effects, bleeding, and a lack of an effective antidote to reverse excessive …

An Updated Examination Of The Perception Of Barriers For Pharmacogenomics Implementation And The Usefulness Of Drug/Gene Pairs In Latin America And The Caribbean, Aimeé Salas-Hernández, Macarena Galleguillos, Matías Carrasco, Andrés López-Cortés, María Ana Redal, Dora Fonseca-Mendoza, Patricia Esperón, Farith González-Martínez, Ismael Lares-Asseff, Alberto Lazarowski, Verónica Loera-Castañeda, Diadelis Remírez, Matías F Martínez, Rodrigo Vargas, Fabricio Rios-Santos, Antonio Macho, Juan P Cayún, Germán R Perez, Carolina Gutierrez, Leslie C Cerpa, Tamara Leiva, Susan Calfunao, Lesly Xajil, Christopher Sandoval, Marcelo Suárez, Ariana Gonzalez, Gabriela Echeverría-Garcés, Luis Sullón-Dextre, Eugenia Cordero-García, Alexis R Morales, Andrea Avendaño, Enrique Sánchez, Laura C Bastone, Cesar Lara, Patricia Zuluaga-Arias, Ana María Soler, Julio Da Luz, Gabriela Burgueño-Rodríguez, Marcelo Vital, Elizabeth Reyes-Reyes, Alexander Huaccha, Yeimy V Ariza, Naomi Tzul, Ana L Rendón, Roberto Serrano, Larissa Acosta, Angelo Motta-Pardo, Leonardo Beltrán-Angarita, Erika Brand, Miguel A Jiménez, Gladys Maribel Hidalgo-Lozada, Marina M J Romero-Prado, Karla Escobar-Castro, Mariel Umaña-Rivas, Juan D Vivas, Paola Lagos, Yineth Ballén Martínez, Sharleth Quesada, Camila Calfio, Maria L Arias, María A Lavanderos, Dante D Cáceres, Alberto Salazar-Granara, Nelson M Varela, Luis A Quiñones

Faculty, Staff and Student Publications

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers …

Structure-Based Rational Design Of Small Α-Helical Peptides With Broad-Spectrum Activity Against Multidrug-Resistant Pathogens, Sandeep Lohan, Anastasia G. Konshina, Roman G. Efremov, Innokentiy Maslennikov, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of small (7–12 mer) amphipathic cationic peptides were designed and synthesized to create short helical peptides with broad-range bactericidal activity and selectivity toward the bacterial cells. The analysis identified a lead 12-mer peptide 8b with broad-spectrum activity against Gram-positive (MIC = 3.1–6.2 μg/mL) and Gram-negative (MIC = 6.2–12.5 μg/mL) bacteria and selectivity toward prokaryotic versus eukaryotic cells (HC50 = 280 μg/mL, >75% cell viability at 150 μg/mL). The rapid membranolytic action of 8b was demonstrated by a calcein dye leakage assay and confirmed using scanning electron microscopy. According to circular dichroism and NMR spectroscopy, the peptides have an …

Targeted Therpeutics For Prostate Cancer, Behind The Scenes Of Psma & Cysteine Protease Trapping Mechanism, Alireza Basiri

Theses & Dissertations

In an attempt to increase the residence time of PSMA-targeted theranostics inside the prostate cancer cells and tumors, we designed and prepared a CPTA-PSMATA resembling PSMA-617 by adding a well-known cysteine protease inhibitor (E-64) to the conjugate. Lysosomal proteases, including cysteine, serine, and aspartic families of hydrolytic enzymes, are expressed in high concentrations in the lysosomes and are responsible for the catabolism of proteins inside the cell [165, 278]. We proposed that after successful internalization of the PSMA-targeted conjugates into the cells, they will be conveyed to the endolysosomes. In these endolysosomal compartments, the E-64 moiety will covalently bind to …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

The Development Of A Novel Peptide-Drug Conjugate For Treating Triple-Negative Breast Cancer, Phi-Phung Than

Pharmaceutical Sciences (MS) Theses

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor prognosis and is difficult to treat. A diagnosis of TNBC means that the three most common types of receptors known to fuel most breast cancer growth–estrogen, progesterone, and HER2– are not present in the cancer tumors. Since the tumor cells lack necessary receptors, common treatments like hormone therapies and targeted HER2 drugs are ineffective. The use of chemotherapies in treating TNBC is an effective option instead. However, chemotherapies are not selective, thus they cause severe side effects such as cardiotoxicity, myelosuppression, alopecia and gastrointestinal problems. A peptide-drug conjugate …

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …

Effects Of Glp-1 Receptor Agonists On Cardiovascular Outcomes In Patients With Type 2 Diabetes And Chronic Kidney Disease: A Systematic Review And Meta-Analysis, Michael Kelly, Jelena Lewis, Hindu Rao, Jessica Carter, Ivan Portillo, Richard Beuttler

College of Pharmacy Faculty Papers

AIM: To evaluate the cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP1-RA) in patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD).

MATERIALS AND METHODS: We searched PubMed, Ovid MEDLINE, CINAHL, and Web of Science databases for randomized controlled trials reporting event rates for a composite cardiovascular outcome of cardiovascular death, myocardial infarction, and stroke in patients with T2DM and CKD receiving GLP1-RA or placebo. Studies were restricted to those reporting specific event rates for patients with CKD separately from the overall population. We conducted a meta-analysis using a random-effects model. This meta-analysis was registered on PROSPERO (CRD42022320157). …

Membrane-Active Cyclic Amphiphilic Peptides: Broad-Spectrum Antibacterial Activity Alone And In Combination With Antibiotics, Eman H. M. Mohammed, Sandeep Lohan, Tarra Ghaffari, Shilpi Gupta, Rakesh K. Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We designed a library of 24 cyclic peptides containing arginine (R) and tryptophan (W) residues in a sequential manner [RnWn] (n = 2–7) to study the impact of the hydrophilic/hydrophobic ratio, charge, and ring size on the antibacterial activity against Gram-positive and Gram-negative strains. Among peptides, 5a and 6a demonstrated the highest antimicrobial activity. In combination with 11 commercially available antibiotics, 5a and 6a showed remarkable synergism against a large panel of resistant pathogens. Hemolysis (HC50 = 340 μg/mL) and cell viability against mammalian cells demonstrated the selective lethal action of 5a against bacteria over …

Protein Phosphatase 2a Regulates Xanthine Oxidase-Derived Ros Production In Macrophages And Influx Of Inflammatory Monocytes In A Murine Gout Model, Sandy Elsayed, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Gout is a common arthritis, due to deposition of monosodium urate (MSU) crystals which results in IL-1β secretion by tissue-resident macrophages. Xanthine oxidase (XO) catalyzes uric acid (UA) production and in the process, reactive oxygen species (ROS) are generated which contributes to NLRP3 inflammasome activation. Protein phosphatase 2A (PP2A) may be involved in regulating inflammatory pathways in macrophages. The objective of this study was to investigate whether PP2A regulates gout inflammation, mediated by XO activity modulation. We studied UA and ROS generations in MSU stimulated murine bone marrow derived macrophages (BMDMs) in response to fingolimod phosphate, a PP2A activator, …

Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method …

Prostate Imaging Reporting And Data System Score (Pi-Rads) And Glutathione S-Transferase P1 Methylation Status (Gst-P1) In The Diagnosis Of Prostate Cancer Patients With Borderline Psa Values, Marius Stan, Vladimir Botnarciuc, Andra Iulia Suceveanu, Andreea Cristina Costea, Adrian Paul Suceveanu, Laura Mazilu, Ciprian Iorga, Tony Hangan, Corneliu Tudor, Dragos Epistatu, Sergiu Chirila, Viorel Gherghina, Felix Voinea

Journal of Mind and Medical Sciences

Objectives. The objective of this study was to evaluate the potential use of Prostate Imaging – Reporting and Data System version 2 (PI-RADS) in combination with Glutathione S-transferase P1 (GST-P1) expression for an improved diagnosis of prostate cancer, in patients with inconclusive values of prostate-specific antigen (PSA). Materials and Methods. The study was conducted on 80 patients for whom PSA values were evaluated and were found to be inconclusive (4-10 ng/ml). These patients underwent imagistic evaluation (PI-RADS), followed by transurethral prostate biopsy, with the evaluation of GST-P1 expression and histopathological examination (for diagnosis confirmation). Results. By combining the results of …

Host-Level Susceptibility And Irf1 Expression Influence The Ability Of Ifn-Γ To Inhibit Kshv Infection In B Lymphocytes, Nedaa Alomari, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi’s sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman’s disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-γ has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, …

Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer’s disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the TNF-α receptor (TNFR), a biologic TNFI that sequesters TNF-α, to a transferrin receptor antibody (TfRMAb) to deliver the TNFI into the brain across the blood–brain barrier (BBB). TfRMAb-TNFR was protective in 6-month-old transgenic APP/PS1 mice in our previous work. However, the effects and safety following delayed chronic TfRMAb-TNFR treatment are unknown. Herein, we initiated the treatment when the male APP/PS1 mice were 10.7 months old (delayed treatment). Mice were injected intraperitoneally with saline, TfRMAb-TNFR, etanercept (non-BBB-penetrating …

Comparative Estimation Of The Cytotoxic Activity Of Different Parts Of Cynara Scolymus L.: Crude Extracts Versus Green Synthesized Silver Nanoparticles With Apoptotic Investigation, Shady Swidan, Amgad Khedr, Abdelaziz Farrag, Ali Nasr, Mohamed Nafie, Maged Abdel-Kader, Marwa Goda, Jihan Badr, Reda Abdelhameed

Pharmacy

Different parts of Cynara scolymus L. and their green synthesized eco-friendly silver nanoparticles (AgNPs) were screened for their cytotoxicity and apoptotic activity. Results showed that flower extract AgNPs exhibited more potent cytotoxicity compared to the normal form against PC-3 and A549 cell lines with IC50 values of 2.47 μg/mL and 1.35 μg/mL, respectively. The results were compared to doxorubicin (IC50 = 5.13 and 6.19 μg/mL, respectively). For apoptosis-induction, AgNPs prepared from the flower extract induced cell death by apoptosis by 41.34-fold change and induced necrotic cell death by 10.2-fold. Additionally, they induced total prostate apoptotic cell death by a 16.18-fold …

Novel Drugs Approved In 2021-2022, Michael Do, Bona Shin, Elaina Lioudis, Emaleigh Munn

Transformative Medicine

This article provides an abbreviated overview of the newly Federal Drug Administration (FDA)approved novel drugs of 2021-2022 with their respective approved indication(s). The FDA serves as the governing body that regularly evaluates and approves medications that will eventually be introduced to the market for routine use. These medications include both drugs that are the same or related to previously approved products (e.g., Extended indications of priorly approved medications) and novel drugs. By definition, a novel drug is an innovative product which serves to improve quality care in patient populations with unmet or advanced medical needs to overall advance patient care …

Silver Nanoparticles Formulation Of Flower Head’S Polyphenols Of Cynara Scolymus L.: A Promising Candidate Against Prostate (Pc-3) Cancer Cell Line Through Apoptosis Activation, Shady Swidan, Amgad Khedr, Marwa Goda, Abdelaziz Farrag, Ali Nasr, Mohamed Nafie, Maged Abdel-Kader, Jihan Badr, Reda Abdelhameed

Pharmacy

Cynara scolymus L. (Family: Compositae) or artichoke is a nutritious edible plant widely used for its hepatoprotective effect. Crude extracts of flower, bract, and stem were prepared and evaluated for their in vitro antioxidant activity and phenolic content. The flower crude extract exhibited the highest phenolic content (74.29 mg GAE/gm) as well as the best in vitro antioxidant activity using total antioxidant capacity (TAC), ferric reducing antioxidant power (FEAP), and 1,1-diphenyl-2-picrylhyazyl (DPPH) scavenging assays compared with ascorbic acid. Phenolic fractions of the crude extracts of different parts were separated and identified using high-performance liquid chromatography HPLC-DAD analysis. The silver nanoparticles …

Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …

Nanotherapeutics And Hiv: Four Decades Of Infection Canvass The Quest For Drug Development Using Nanomedical Technologies, Bhupender S. Chhikara, Nirpendra Singh, Poonam, Parveen Bazard, Rajender S. Varma, Keykavous Parang

Pharmacy Faculty Articles and Research

We have seen four decades of human struggle to cure or eradicate HIV infection since the first clinical detection of HIV infection. Various developed drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, microbicides, and others have known restrictions, such as side effects and resistance development when used alone, and hidden reservoir of the virus, which have opened the gates for the involvement of nanomedicine associated systems, particularly for latent sites of HIV infection. The nanotechnological vehicles, such as liposomes, dendrimers, metal nanoparticles, polymeric nanocapsules/particles, surfactants, and targeted vehicles have become part …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

10-Minute Ebd: Stimulant Medications, Rampant Caries, And Prevention, Madison Thomas Bs, Nancy Poznick Dds, Melanie E. Mayberry Dds, Ms-Hcm

The Journal of the Michigan Dental Association

The 10-Minute Evidence-Based Dentistry Column illustrates how to implement the evidence-based dentistry search process to quickly identify and apply the best literature to answer a clinical question. Through critical appraisal, the author of this article answers the clinical question of a connection between stimulant medications, rampant caries, and prevention, with a focus on the impact of ADHD medication on oral health. The term "meth mouth" often associated with dental decay is discussed in the context of xerostomia (dry mouth), a common side effect of stimulant medications. The article uses the PICO (Population, Intervention, Comparison, Outcome) system to formulate a research …

Jatropha Tanjorensis A Flora Of Southeast Nigeria: Isolation And Characterization Of Naringenin And Validation Of Bio-Enhanced Synergistical Activity Of Α- Tocopherol Toward Clinical Isolates Of Resistant Bacterial, Ikechukwu Kingsley Ijoma, Vincent Ishmael Egbulefu Ajiwe

Makara Journal of Science

Jatropha tanjorensis is among the rich floras of Southeast Nigeria and used by ethnic people to treat infections and manage health conditions. Ethnomedicine has long been employed in the treatment of ailments caused by bacterial pathogens. Studies showed that the incorporation of synthetic α-tocopherol to an antibacterial agent improves its activity. However, knowledge about the antibacterial-enhanced activity of plant-based α-tocopherols, especially those isolated from Jatropha tanjorensis, is limited because of the different bioactivities of synthetic and natural α-tocopherols. To determine the phytochemicals in J. tanjorensis, we carried out the structural elucidation of its leaf extracts. Naringenin and α-tocopherol …

Channelopathy Of Small- And Intermediate-Conductance Ca2+-Activated K+ Channels, Young-Woo Nam, Myles Downey, Mohammad Asikur Rahman, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca²⁺-activated K⁺ (K_Ca2.x/K_Ca3.1 also called SK/IK) channels are gated exclusively by intracellular Ca²⁺. The Ca²⁺ binding protein calmodulin confers sub-micromolar Ca²⁺ sensitivity to the channel-calmodulin complex. The calmodulin C-lobe is constitutively associated with the proximal C-terminus of the channel. Interactions between calmodulin N-lobe and the channel S4-S5 linker are Ca²⁺-dependent, which subsequently trigger conformational changes in the channel pore and open the gate. KCNN genes encode four subtypes, including KCNN1 for K_Ca2.1 (SK1), KCNN2 for K_Ca2.2 (SK2), KCNN3 for K …

Channelopathy Of Small- And Intermediate-Conductance Ca2+-Activated K+ Channels, Young-Woo Nam, Miles Downey, Mohammad Asikur Rahman, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca²⁺-activated K⁺ (K_Ca2.x/K_Ca3.1 also called SK/IK) channels are gated exclusively by intracellular Ca²⁺. The Ca²⁺ binding protein calmodulin confers sub-micromolar Ca²⁺ sensitivity to the channel-calmodulin complex. The calmodulin C-lobe is constitutively associated with the proximal C-terminus of the channel. Interactions between calmodulin N-lobe and the channel S4-S5 linker are Ca²⁺-dependent, which subsequently trigger conformational changes in the channel pore and open the gate. KCNN genes encode four subtypes, including KCNN1 for K_Ca2.1 (SK1), KCNN2 for K_Ca2.2 (SK2), KCNN3 for K …

Stereocontrolled Access To Δ-Lactone-Fused-Γ-Lactams Bearing Angular Benzylic Quaternary Stereocenters, Timothy K. Beng, Morgan J. Rodriguez, Claire Borg

All Faculty Scholarship for the College of the Sciences

C-fused γ-lactam-lactones are resident in several bioactive molecules, including anticancer agents such as omuralide. In this embodiment, we report mild conditions for the catalytic halolactonization of lactam-tethered 5-aryl-4(E)-pentenoic acids. The use of dichloromethane as the solvent and Ph₃PS as the catalyst led to predominant 6-endo-trig cyclization and furnished the trans-fused-γ-lactam-δ-lactones. The transformation is modular, regioselective, chemoselective, and diastereoselective. The γ-lactam-δ-lactones bear angular quaternary benzylic stereocenters, which is noteworthy since the presence of a quaternary carbon in bioactive small molecules often promotes an element of conformational restriction that imparts potency, selectivity, and metabolic stability. The …