Medicinal and Pharmaceutical Chemistry Commons^™

A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …

A Novel Hplc Method For Determination Of Phenytoin In Human Plasma, Jesse Flores, Sheril Alexander, Mariana Babayeva

Touro College of Pharmacy (New York) Publications and Research

Aim: Aim of this research was to develop and validate a simple, efficient and reproducible high performance liquid chromatography method to measure phenytoin concentrations in human plasma

Study Design: Linearity, selectivity, sensitivity, accuracy and precision of the analytical methods were validated according to ICH guidelines.

Methodology: The method employed a Phenomenex C18 column kept at 25ºC. The mobile phase consisted of a 0.05 M potassium dihydrogen phosphate buffer solution (pH 2.8) and methanol in a ratio of 60:40, respectively. The flow rate of the mobile phase was 0.7 mL/min. Phenytoin was detected at a wavelength of 250 …

Incidence, Risk Factors, And Prediction Of Gastrointestinal And Intracranial Bleeding In A Cohort Of Older Veterans Prescribed Oral Anticoagulants, Angela Laurio

Dissertations and Theses

ABSTRACT

Incidence, Risk Factors, and Prediction of Gastrointestinal and

Intracranial Bleeding in a Cohort of Older Veterans Prescribed Oral Anticoagulants

by

Angela L. Laurio

Advisor: Marianne (Mimi) C. Fahs, PhD, MPH

Objectives:

The objectives of this dissertation were to: (1) describe and compare the incidence and odds of gastrointestinal and intracranial bleeding in veterans age 50 to 89 who were prescribed warfarin, direct oral anticoagulants, or no oral anticoagulants; (2) identify risk factors for gastrointestinal and intracranial bleeding among older veterans prescribed oral anticoagulants, and to calculate the relative risk of bleeding over time through time-to-event analysis; and (3) develop …

Assessing Vancomycin Dosing Per Pharmacy In Elderly Patients Over The Age Of 74 Years, Lee H. Nguyen, Martin Breen, Jason Yamaki, Geraldine Cadalin, Nilomi Shah, Linda Lumintaintang

Pharmacy Faculty Articles and Research

Vancomycin has a complex pharmacokinetic profile and carries potential risks for nephrotoxicity and ototoxicity. The pharmacokinetic profile in elderly patients significantly differs from that of younger patients. It is common practice in many institutions for pharmacists to intentionally round serum creatinine levels to 1 mg/dl in elderly patients with levels <1 mg/ dl to avoid overestimating clearance and toxicities. This can potentially lead to underestimation of creatinine clearance, and subsequently lead to vancomycin under dosing. The aim of this study was to evaluate vancomycin target trough attainment and the time to trough attainment with vancomycin dosing per pharmacy in elderly patients.

Site-Selective Modification Of Peptides And Proteins Via Organocatalyzed Henry Reaction, Zilma Pereira Muneeswaran

Seton Hall University Dissertations and Theses (ETDs)

In this research, peptides and protein containing serine on the N-terminus underwent site-selective modification following organocatalyzed bioconjugation that offered an additional functional group. It was shown that transforming the N-terminus serine to an aldehyde allowed site-specific bioconjugation to occur by utilizing the well-known Henry reaction. This method also grants a safer pathway for bioconjugation utilizing “green-chemistry” and biocompatible conditions. Amino acids and amino acid derived organocatalysts were utilized in the Henry reaction resulting in yields of up to 86 % conversion. Promising preliminary results were achieved in this research using peptides and myoglobin as the bioconjugation targets. Further investigation to …

Synthesis Of Novel 5-Substituted Pyrrolo[2,3-D]Pyrimidine Antifolates As Selective And Potent Anti-Tumor Agents, Mohammad Karim

Electronic Theses and Dissertations

In last few decades many folate analogs have been discovered and several compounds are successfully being used as anticancer agents. Methotrexate (MTX), pemetrexed (PMX), raltitrexed (RTX): are a few examples of classical antifolates that are currently in clinical use. Although these compounds are widely used, all of them show dose limiting toxicity due to their non-specific transport into normal cells as well as malignant cells. Currently, clinically used classical antifolates suffer from this disadvantage because there is no way to selectively transport them into malignant cells. Currently available antifolates are transported via reduced folate career (RFC) as well as Folate …

Next Generation Of Translational Long-Acting Cabotegravir, Tian Zhou

Theses & Dissertations

Recent development of long-acting antiretroviral therapeutic regimens has opened a new chapter for HIV/AIDS management. Cabotegravir (CAB), as one of the very first long-acting antiretroviral regimens, has drawn tremendous attention. However, the remaining challenges include suboptimal dosing intervals, large injection volume, injection site reactions, lack of tissue penetration, etc. As one of the pioneers in this field, our lab was successful in harnessing mononuclear phagocytes as “Trojan horses” for antiretroviral drug delivery and transportation to viral reservoirs. We proposed this targeted delivery strategy could address the limitations of current CAB formulation. To this end, we developed folic acid decorated CAB …

A Time Course Study Of Rotavirus-Infected Intestinal Cells Treated With Stilbenoids And The Regulation Of Apoptosis, Rebecca D. Parr, Caleb M. Witcher, Rebekah Napier-Jameson, Hannah L. Wilson, Stormey Wisdom, Macie N. Mattila, Essence B. Strange, Josephine Taylor, Beatrice Clack, Fabricio Medina-Bolivar, Judith M. Ball

Faculty Publications

This is a time course study of virus –host interactions that are modified with the addition of two small natural products. They appear to effect virus replication and the host response to the infection.

Synthesis And Cytotoxicity Of Azaheterocyclic Compounds, Keyur M. Pandya

Theses and Dissertations

Multicomponent coupling reactions (MCRs) have been known for a long time and one such reaction that utilizes isocyanides is Passerini reaction. It is a powerful tool to synthesize libraries of different compounds. Azaheterocyclic compounds play an important role in medicinal chemistry. Motifs such as imidazoles, piperazines, pyrazoles, pyridines, triazoles, etc. are routinely observed in several compounds of pharmacological interest. Several natural products also contain these motifs in them. We have undertaken a library synthesis of heterocyclic molecules driven by our group's long-standing interest of synthesizing medicinally relevant small molecules employing green chemistry techniques.

This thesis details our efforts on the …

Characterization Of The Hepatotoxicity Of Rifampicin And Isoniazid, Christopher T. Brewer

Theses and Dissertations (ETD)

In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase of protoporphyrin ix (PPIX), the penultimate heme precursor. Excess PPIX is believed to bind to bile acids, precipitate in bile canaliculi, and form bile plugs leading to cholestasis fol owed by liver injury. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to up-regulate Alas1 but down-regulate Fech protein levels in mice; however the mechanism of isoniazid mediated heme synthesis …

Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley

Theses and Dissertations (ETD)

Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - …

Linear Ubiquitin Chain-Binding Domains, Lilian Fennell, Simin Rahighi, Fumiyo Ikeda

Pharmacy Faculty Articles and Research

Ubiquitin modification (ubiquitination) of target proteins can vary with respect to chain lengths, linkage type, and chain forms, such as homologous, mixed, and branched ubiquitin chains. Thus, ubiquitination can generate multiple unique surfaces on a target protein substrate. Ubiquitin‐binding domains (UBDs) recognize ubiquitinated substrates, by specifically binding to these unique surfaces, modulate the formation of cellular signaling complexes and regulate downstream signaling cascades. Among the eight different homotypic chain types, Met1‐linked (also termed linear) chains are the only chains in which linkage occurs on a non‐Lys residue of ubiquitin. Linear ubiquitin chains have been implicated in immune responses, cell death …

A Study Of Albendazole And Artemisinin Drugs Under Electrochemical Oxidation, Zahilis A. Mazzochette

Theses and Dissertations

This work is aimed to investigate the metabolic behavior of albendazole and artemisinin. The electrochemical oxidation and reduction of these drugs were performed on electrode materials to mimic their metabolism in vivo using cyclic voltammetry and bulk electrolysis analysis. The oxidation of albendazole on gold electrode surface yielded albendazole sulfoxide and albendazole sulfone which are the main metabolites of this drug in vivo. Reduction of artemisinin on glassy carbon (GC) electrode surface yielded dihydroartemisinin and deoxy artemisinin. The formation of these products was monitored using liquid chromatography and mass spectrometry techniques. The redox processes for both drugs were shown to …

Refrigerated Stability Of Diluted Cisatracurium, Rocuronium, And Vecuronium For Skin Testing After Perioperative Anaphylaxis, Kristen Dinsmore, Bethany Campbell, Timothy Archibald, Greg Mosier, Stacy Brown Phd, Alexei Gonzalez-Estrada Md

Appalachian Student Research Forum

Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing.

Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions.

Results: The results …

Do Paraben Derivatives Alter T Cell Immunity?, Hailey Kintz

Spring Presentation of Undergraduate Research

T cells immunity is linked to a complex system of cytokines that determine differentiation of naïve T cells into Th1, Th2, Th17, and Treg cells. Estrogen production or periods of elevated production have been correlated with an anti-inflammatory state in which Th2 and Treg cells are up-regulated. Such responses in the immune system are capable of supporting pre-cancerous activity. We are investigating the tie between the xenoestrogen compounds found in cosmetics, parabens, and their ability to regulate T cell immunity. Testing parabens and paraben derivatives with weaker estrogen receptor association will allow for a better understanding of the interplay between …

Analyzing The Differentiation Among State Medical Marijuana Policies By Examining State Policies & Trends, Richard Furlong

Political Science Theses and Capstones

Support for marijuana has been growing nationwide. This increased support has gained a lot of momentum since the late 1990s when California became the first state to legalize marijuana for medical use by enacting Proposition 215, or the Compassionate Use Act. Since the enactment of Proposition 215, 28 more states and the District of Columbia have legalized marijuana for medicinal use. I look into why states have begun to adopt these laws, and what makes these states differ throughout the country in the timeliness of their actions. I assembled data to examine a variety of state policies to attempt to …

Novel Aminobenzoboroxoles As Potential Anti-Cancer Agents, Bhawankumar Pravinchandra Patel

Theses and Dissertations

Boronic acids are a promising class of compounds due to their wide range of applications in medicinal and materials chemistry, and as coupling agents in organic synthesis. B-hydroxy-1,2-oxaborolanes (benzoboroxoles) are categorized as cyclic boronic acid derivatives and they are very important organic molecules because of their metabolic stability and their ability to undergo important C-C bond forming reactions such as Suzuki cross coupling. Several of these cyclic boronic acids are found to have promising pharmacological properties as antifungal, antimalarial and anti-inflammatory agents. However, based on the literature reports, synthesis of highly functionalized benzoboroxoles is typically cumbersome and not very conducive …

Topical Digitoxigenin For Wound Healing: A Feasibility Study, Xinchi Feng, Cuifen Wang, Yunhui Xu, Joel Turley, Zijian Xie, Sandrine Pierre, Jinsong Hao

Pharmaceutical Science and Research

(1) Background: Cardiotonic steroids have been found to stimulate collagen synthesis and might be potential wound healing therapeutics. The objective of this study was to evaluate the feasibility of digitoxigenin and its topical formulation for wound healing; (2) Methods: In the in vitro study, the human dermal fibroblast cells were treated with digitoxigenin and collagen synthesis was assessed. In the in vivo study, digitoxigenin was applied to excisional full-thickness wounds in rats immediately after wounding and remained for three days, and wound open was evaluated over 10 days. A digitoxigenin formulation for topical administration was prepared, and the in vitro …

Synthesis, Characterization, And In Vitro Cytotoxicity Of Fatty Acyl-Cgkrk-Chitosan Oligosaccharides Conjugates For Sirna Delivery, Naglaa Salem El-Sayed, Meenakshi Sharma, Hamidreza Montazeri Aliabadi, Magda Goda El-Meligy, Ahmed Kamed El-Zaity, Zenat Adeeb Nageib, Rakesh Tiwari

Pharmacy Faculty Articles and Research

In this studies, three fatty acyl derivatives of CGKRK homing peptides were coupled successfully to chitosan oligosaccharides (COS) using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate sodium salt (sulfo-SMCC). The COS-SMCC was prepared by direct coupling between COS and sulfo-SMCC in PBS (pH 7.5) at RT for 48 h. The structure of COS-SMCC and the three fatty acyl-CGKRK-SMCC-COS conjugates were characterized by FT-IR, ¹³C NMR, and SEM. The ability of three conjugates to condense siRNA into nanosized polyplexes and their efficacy in protecting siRNA from serum nucleases degradation were investigated. Among the investigated derivatives, S-CGKRK-COS showed higher siRNA binding affinity as compared to …

Cost-Effectiveness Analysis Of Metformin+Dipeptidyl Peptidase-4 Inhibitors Compared To Metformin+Sulfonylureas For Treatment Of Type 2 Diabetes, Christina S. Kwon, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

Background: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D.

Methods: …