Medicinal-Pharmaceutical Chemistry Commons^™

Apoptotic And Chemotherapeutic Properties Of Iron (Iii)-Salophene In An Ovarian Cancer Animal Model, Thilo S. Lange, Carolyn Mccourt, Rakesh K. Singh, Kyu Kwang Kim, Ajay P. Singh, Brian S. Luisi, Onur Alptürk, Robert M. Strongin, Laurent Brard

Chemistry Faculty Publications and Presentations

The cytotoxicity of organometallic compounds iron(III)-, cobalt(III)-, manganese(II)-, and copper(II)-salophene (-SP) on platinum-resistant ovarian cancer cell lines was compared. Fe-SP displayed selective cytotoxicity (IC(50) at ~1 muM) against SKOV-3 and OVCAR-3 cell lines while Co-SP caused cytotoxic effects only at higher concentrations (IC(50) at 60 muM) and Cu-SP effects were negligible. High cytotoxicity of Mn-SP (30-60 muM) appeared to be nonspecific because the Mn-chloride salt reduced cell viability similarly. The effect of Fe-SP at 1 muM proved to be ovarian cancer cell selective when compared to a panel of cell lines derived from different tumors. The first irreversible step in …

Identifying Biomarkers For Resistance To Novel Cisplatin Analogues In Human Lung, Breast And Prostate Cancers, Becky Michelle Hess

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cisplatin is a common therapeutic agent used in cancer treatment. Unfortunately, resistance to cisplatin in addition to severe side effects limits its use in cancer treatment. Two novel cisplatin analogues, 4DB and 4TB were shown to have varying cytotoxicity in lung, breast and prostate cancer cells. The hypothesis for this study states that the differences in 4DB and 4TB cytotoxicity among different tissue types is due to the type and efficiency of DNA repair mechanisms involved in response to these drugs.

To test the hypothesis, proteins involved in the rate limiting step of nucleotide excision repair (NER) and mismatch repair …

Controlled Assembly Of Rodlike Viruses With Polymers, Tao Li, Laying Wu, Nisaraporn Suthiwangcharoen, Michael A. Bruckman, Dayton Cash, Joan S. Hudson, Soumitra Ghoshroy, Qian Wang

Faculty Publications

A practical method to assemble rodlike tobacco mosaic virus and bacteriophage M13 with polymers was developed, which afforded a 3D core–shell composite with morphological control.

Immobilization Method For Producing Active Α1-Acid Glycoprotein, David S. Hage, Hai Xuan

Department of Chemistry: Faculty Publications

A method and kit for immobilization of a glycoprotein. The method may include activating an affinity Support. The affinity Support may be activated by reacting the affinity Support with a compound that is reactive with one or more functional groups included within the glycoprotein. The method may also include oxidizing the glycoprotein in which oxidation conditions are selected to yield an oxidized glycoprotein that is biologically active and contains a Sufficient number of reactive aldehyde groups for coupling to a Support. For example, the oxidized glycoprotein may include five reactive aldehyde groups. In addition, the method may include reacting the …

Preparation And Characterization Of Some Substituted Benzyl N-Nitrosocarbamates Containing An N-2-(Methylthio)Ethyl Or A Bis(2-Aminoethyl)Sulfide Functionality, Satya Venkata, Eric Shamo, Vladimir Benin

Chemistry Faculty Publications

The synthesis and characterization of some substituted benzyl N-nitrosocarbamates with an N-2-(methylthio)ethyl or a bis(2-aminoethyl)sulfide functionality is reported, as a part of a long-term goal to design and prepare novel photolabile structures that could be used as substances for controlled release of alkylating and/or crosslinking agents. The synthesis was accomplished by reaction of benzyl chloroformates with the corresponding amines, resulting in the preparation of carbamates. The latter were subsequently nitrosated, utilizing two different N-nitrosation methods, to yield the target structures.

Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar

Pharmacy Faculty Articles and Research

A specific and sensitive liquid chromatography (LC)-tandem mass spectrometric method for quantitative determination of methylprednisolone (MP) in rat plasma and liver was developed and validated using triamcinolone acetonide as an internal standard. Liquid-liquid extraction using tert-butyl methyl ether was used to extract the drug and the internal standard from plasma and liver. The separation of MP was performed on a C(18) column with a mobile phase of acetonitrile:0.5% formic acid aqueous solution (85:15, v/v) over 4 min. The assay was based on the selected reaction monitoring transitions at m/z 375 -> 161 for MP in plasma, 375 -> 357 for …

Androgen-Stimulated Udp-Glucose Dehydrogenase Expression Limits Prostate Androgen Availability Without Impacting Hyaluronan Levels, Qin Wei, Robert Galbenus, Ashraf Raza, Ronald Cerny, Melanie A. Simpson

Ronald Cerny Publications

UDP-glucose dehydrogenase (UGDH) oxidizes UDP-glucose to UDP-glucuronate, an essential precursor for production of hyaluronan (HA), proteoglycans, and xenobiotic glucuronides. High levels of HA turnover in prostate cancer are correlated with aggressive progression. UGDH expression is high in the normal prostate even though HA accumulation is virtually undetectable. Thus, its normal role in the prostate may be to provide precursors for glucuronosyltransferase enzymes, which inactivate and solubilize androgens by glucuronidation. In this report, we quantified androgen dependence of UGDH, glucuronosyltransferase, and HA synthase expression. Androgen dependent and independent human prostate cancer cell lines were used to test the effects of UGDH …

A Multi-Step Nmr Screen For The Identification And Evaluation Of Chemical Leads For Drug Discovery, Kelly A. Mercier, Matthew D. Shortridge, Robert Powers

Department of Chemistry: Faculty Publications

A multi-step NMR based screening assay is described for identifying and evaluating chemical leads for their ability to bind a target protein. The multi-step NMR assay provides structure-related information while being an integral part of a structure based drug discovery and design program. The fundamental principle of the multi-step NMR assay is to combine distinct 1D and 2D NMR techniques, in such a manner, that the inherent strengths and weakness associated with each technique is complementary to each other in the screen. By taking advantage of the combined strengths of 1D and 2D NMR experiments, it is possible to minimize …

Anhydrous Fluoride Salts And Reagents And Methods For Their Production, Stephen G. Dimagno, Haoran Sun

Department of Chemistry: Faculty Publications

Anhydrous organic fluoride salts and reagents prepared by a method comprising the nucleophilic Substitution of a fluorinated aromatic or fluorinated unsaturated organic compound with a salt having the formula: [Q_nM]^x+A_x^- in an inert polar, aprotic solvent; wherein M is an atom capable of supporting a formal positive charge, the n groups Q are independently varied organic moieties, n is an integer such that the [Q_nM] carries at least one formal positive charge, x is an integer defining the number of formal positive charge(s), +, carried by the [Q_nM], A^{- …}

Generation Of Novel Pikromycin Antibiotic Products Through Mutasynthesis, Shuchi Gupta, Venkatraman Lakshmanan, Beom Seok Kim, Robert Fecik, Kevin A. Reynolds

Chemistry Faculty Publications and Presentations

Mutasynthesis in pikromycin PKS: The amenability of pikromycin polyketide synthase to mutational biosynthesis has been demonstrated. A natural triketide and its analogues, activated as N-acetyl-cysteamine thioesters, were synthesized and fed to a pikAI-deleted strain; this led to the production of new antibiotics. A vinyl analogue was found to have better antibacterial activity than pikromycin.

Preliminary Development Of Quantitative Immunoassays For Mitochondrial Proteins, Adriann Hovey

Honors Program Theses

Mitochondria are medium-sized organelles in which most cellular metabolic reactions are carried out. In postmitotic cells that are aged or diseased, such as myocardial, skeletal, and brain cells, abnormally large mitochondria ("giant mitochondria") are often observed. Mitochondrial size and shape are controlled by mitochondrial fusion and fission and disruption of this process may lead to their abnormally large size (Nauratil, Terman, Arriaga, 2008). These giant mitochondria exhibit variations from normal metabolism and altered membrane potentials (Nauratil et al., 2008). An increased number of giant mitochondria may therefore disrupt cell function (Nauratil et al., 2008). This accumulation may result either from …