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Medicinal-Pharmaceutical Chemistry Commons

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2010

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Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Structure-Based Design Of Inhibitors Targeting Influenza A Virus M2 Proton Channel (A/M2), Jun Wang Dec 2010

Structure-Based Design Of Inhibitors Targeting Influenza A Virus M2 Proton Channel (A/M2), Jun Wang

Publicly Accessible Penn Dissertations

Influenza A virus M2 (A/M2) forms a homotetrameric channel in viral membranes that is highly selective for protons. A/M2 has been extensively studied by electrophysiologists, biophysicists, structural biologists and biochemists in order to understand the mechanism and selectivity of proton conductance from the structural basis. Medicinal chemists have also studied A/M2 as therapeutic target for anti-flu drugs. However, research on A/M2 drug binding lead to entirely different binding sites of two very similar anti-flu drugs. In light of the urgency in developing novel antivirals against drug resistant A/M2 mutants, it is imperative to solve this ...


Novel Amino Acid And Ethanolamine Derivatives As Potential Tumor Imaging Agents For Positron Emission Tomography, Limin Wang Dec 2010

Novel Amino Acid And Ethanolamine Derivatives As Potential Tumor Imaging Agents For Positron Emission Tomography, Limin Wang

Publicly Accessible Penn Dissertations

Malignant tumors can be detected with high sensitivity and specificity by imaging their increased metabolic rate for glucose, amino acids and fatty acids. Positron emission tomography (PET) with glucose analog [18F]FDG, which utilizes increased glucose metabolism, has become a routine clinical test for diagnosis, staging and restaging a variety of cancers. Despite the tremendous success of PET-FDG, there are some well-known limitations of [18F]FDG such as high cerebral uptake, uptake in inflammatory tissues, high excretion through urinary tract and low or negligent uptake in certain type of tumors. Decades of nuclear medicine research have lead to development of ...


New Cyclic Peptides Via Ring-Closing Metathesis Reactions And Their Anti-Bacterial Activities, Timothy P. Boyle, John B. Bremner, Jonathan Coates, John Deadman, Paul A. Keller, Stephen G. Pyne, David I. Rhodes Aug 2010

New Cyclic Peptides Via Ring-Closing Metathesis Reactions And Their Anti-Bacterial Activities, Timothy P. Boyle, John B. Bremner, Jonathan Coates, John Deadman, Paul A. Keller, Stephen G. Pyne, David I. Rhodes

Paul Keller

As part of a program investigating cyclic peptides with an internal aromatic hydrophobic scaffold as potential novel anti-bacterial agents, we explored the synthesis of simple tyrosine-based systems. These were prepared via key intermediates containing internal allylglycine and allyltyrosine residues for subsequent ring closing metathesis reactions. Although the resulting anti-bacterial activity against Staphylococcus aureus was modest, this represents a novel and simple route to this class of compounds. One intermediate acyclic dipeptide precursor showed good activity against S. aureus with an MIC of 7.8 µg/mL.


A Convenient And Efficient Synthesis Of (S)-Lysine And (S)-Arginine Homologues Via Olefin Cross-Metathesis, Timothy P. Boyle, John B. Bremner, Jonathan A. Coates, Paul A. Keller, Stephen G. Pyne Aug 2010

A Convenient And Efficient Synthesis Of (S)-Lysine And (S)-Arginine Homologues Via Olefin Cross-Metathesis, Timothy P. Boyle, John B. Bremner, Jonathan A. Coates, Paul A. Keller, Stephen G. Pyne

Paul Keller

A convenient five step synthesis of (S)-homolysine, incorporating a key olefin cross-metathesis step in the chain extension methodology, has been developed, together with a six step related synthesis of a new homologue of arginine, (S)-bishomoarginine.


Antimalarial Activity Of 2,4-Diaminopyrimidines, J. Morgan, R. Haritakul, Paul A. Keller Aug 2010

Antimalarial Activity Of 2,4-Diaminopyrimidines, J. Morgan, R. Haritakul, Paul A. Keller

Paul Keller

A series of 2,4- and 4,6-diaminopyrimidines were prepared and evaluated for their in vitro antimalarial activity. Of the 12 compounds tested 7 showed reasonable activity with 1 having a sub-micromolar IC50.


Combining Structure-Based Drug Design And Pharmacophores, Renate Griffith, T. T. T. Luu, James A. Garner, Paul A. Keller Aug 2010

Combining Structure-Based Drug Design And Pharmacophores, Renate Griffith, T. T. T. Luu, James A. Garner, Paul A. Keller

Paul Keller

Development towards integrated computer-aided drug design methodologies is presented by utilising crystal structure complexes to produce structure-based pharmacophores. These novel pharmacophores represent the ligand features that are involved in interactions with the target protein, as well as the space around the ligand occupied by the protein. The protein-ligand complexes can also yield information about all interactions that ligands could potentially form with the binding site, as well as about the size of the binding cavity. Together, these describe a 'superligand', which can also be viewed as a pharmacophore. Various types of novel pharmacophores are discussed and compared, using HIV-1 Reverse ...


Synthesis Of Novel Aromatic Quinols For Colon And Renal Cancers, Bradley J. Davey, Tae Soo Jo, Pradip K. Bhowmik Aug 2010

Synthesis Of Novel Aromatic Quinols For Colon And Renal Cancers, Bradley J. Davey, Tae Soo Jo, Pradip K. Bhowmik

Undergraduate Research Opportunities Program (UROP)

Colon Cancer: The third most common cancer in USA. More than 1 million Americans currently living with colon cancer. 148,810 new cases expected in 2010. 50,000 deaths annually.

Renal Cancer: Approximately 58,000 people diagnosed in USA annually. Seventh most common cancer and tenth most common cause of cancer related death in men.

Aromatic quinols have demonstrated in vitro antitumor activity. Three heteroaromatic quinols show antitumor activity.


Synthesis Of Bis-Styrylbenzene Derivatives Via Wittig-Horner Reaction, Joseph K. Wray, Tae Soo Jo, Pradip K. Browmik Aug 2010

Synthesis Of Bis-Styrylbenzene Derivatives Via Wittig-Horner Reaction, Joseph K. Wray, Tae Soo Jo, Pradip K. Browmik

Undergraduate Research Opportunities Program (UROP)

Alzheimer’s Disease is now one of the most common diseases affecting the elderly population. Recently, bis-styrylbenzene derivatives have been shown to reduce the formation of Beta-amyloid plaques in the brain which are profoundly correlated with this disease. Finding new biologically active compounds which can reduce or prevent Alzheimer’s Disease has drawn much attention over the past few decades. Georg Wittig, Nobel Prize Winner in Chemistry, 1979.


Determining The Activity Of Three Hdac Variants In The Presence Of Compounds Containing 1,2,3-And 1,2,4-Triazoles As Zinc Binding Groups, Rachel Louise Glazener Aug 2010

Determining The Activity Of Three Hdac Variants In The Presence Of Compounds Containing 1,2,3-And 1,2,4-Triazoles As Zinc Binding Groups, Rachel Louise Glazener

Masters Theses

Histone Deacetylase (HDAC) plays a vital role in cellular processes, for example gene expression, cell growth, and apoptosis. Finding drug candidates to inhibit the over activity of HDACs in cancer is a growing area of interest. Inhibitors, thus far, have three important motifs to be studied: the zinc binding group, a hydrophobic linker, and a cap group. By altering these groups on the inhibitor, not only can activity be increased but also selectivity within the classes of HDACs. We present the design of two novel sets of molecules that contain either a 1,2,3-triazole or 1,2,4-triazole. The ...


Developing Of Germyldesulonylation And Thiodesulfonylation Reactions For The Synthesis Of Novel Nucleoside Analogues. Efficient Synthesis Of Novel (Α-Fluoro)Vinyl Sulfides, Pablo R. Sacasa Jr Jul 2010

Developing Of Germyldesulonylation And Thiodesulfonylation Reactions For The Synthesis Of Novel Nucleoside Analogues. Efficient Synthesis Of Novel (Α-Fluoro)Vinyl Sulfides, Pablo R. Sacasa Jr

FIU Electronic Theses and Dissertations

S-adenosyl-L-homocysteine (AdoHcy) hydrolase effects hydrolytic cleavage of AdoHcy to produce both adenosine and L-homocysteine and is a feedback inhibitor of S-adenosyl-L-methionine (SAM). Nucleoside analogues bearing an alkenyl or fluoroalkenyl chain between sulfur and C5′ utilizing Negishi coupling reactions were synthesized. Palladium-catalyzed cross-coupling between the 5′-deoxy-5′-(iodomethylene) nucleosides and alkylzinc bromides gives analogues with the alkenyl unit. Palladium-catalyzed selective monoalkylation of 5′-(bromofluoromethylene)-5′-deoxy-adenosine with alkylzinc bromide afford adenosylhomocysteine analogues with a 6′-(fluoro)vinyl motif. The vinylic adenine nucleosides produced time-dependent inactivation of the S-adenosyl-L-homocysteine hydrolases. Stannydesulfonylation reaction is a critical step in the synthesis of E-fluorovinyl cytidine ...


Research In Natural Product Chemistry, Nathan Krause May 2010

Research In Natural Product Chemistry, Nathan Krause

Student Scholarship - Chemistry

Natural product chemistry is a branch of chemistry that deals with the isolation, identification, and study of the chemical characteristics of chemical substances produced by living organisms. The southwestern United States has a variety of indigenous plants many of which have not been investigated for their chemical compounds but have Native American herbal uses. The aim of this summer internship was to do extractions on plants and test them for medical potential.


Antimicrobial Activity Of D-Lenolate®, Andy Phui May 2010

Antimicrobial Activity Of D-Lenolate®, Andy Phui

UNLV Theses, Dissertations, Professional Papers, and Capstones

Olive trees are one of the most important fruit trees in the Mediterranean. Although not validated by research, olive leaves are traditionally believed to fight off fever and infections. It has been shown that olive leaf extracts possess antimicrobial activity. Olive leaf extracts contain polyphenols. One of the major phenolic compounds is oleuropein. Oleuropein and other polyphenols have been shown to exhibit antimicrobial activity. East Park Research (EPR) developed an extraction process that they claim does not alter the chemical composition of the olive leaves. The extract is known by the commercial name d-lenolate®. Studies have provided evidence that d-lenolate ...


Developing A Biosensor For The Detection Of Bacteria: A Comparison Of Methods For Isolating Bacteria-Specific Antibodies, Scott Allen Walper May 2010

Developing A Biosensor For The Detection Of Bacteria: A Comparison Of Methods For Isolating Bacteria-Specific Antibodies, Scott Allen Walper

Dissertations

The antigen-antibody interaction is known to be a high affinity and highly specific interaction that can readily be used for the detection and identification of biological and chemical agents. These studies were conducted to develop an efficient and cost-effective method of obtaining bacteria-specific antibody molecules for integration into a fielddeployable biosensor. Antigen-binding molecules were obtained both as full-length IgG molecules from a hybridoma cell line and as recombinant single-chain Fv (scFv) antibodies isolated from naïve and immunize libraries. Monoclonal and recombinant antibody systems were compared on the effectiveness of producing new, target-specific molecules; the efficiency of production and purification of ...


Development Of A Scanning Angle Total Internal Reflection Raman Spectrometer, Kristopher J. Mckee, Emily A. Smith Apr 2010

Development Of A Scanning Angle Total Internal Reflection Raman Spectrometer, Kristopher J. Mckee, Emily A. Smith

Chemistry Publications

A scanning angle total internal reflection (SATIR) Raman spectrometer has been developed for measuring interfacial phenomena with chemical specificity and high axial resolution perpendicular to the interface. The instrument platform is an inverted optical microscope with added automated variable angle optics to control the angle of an incident laser on a prism/sample interface. These optics include two motorized translation stages, the first containing a focusing lens and the second a variable angle galvanometer mirror. The movement of all instrument components is coordinated to ensure that the same sample location and area are probed at each angle. At angles greater ...


The Reaction Of A Water Soluble Platinum Compound With Methionine And Derivatives, Yueh Ying Liao Apr 2010

The Reaction Of A Water Soluble Platinum Compound With Methionine And Derivatives, Yueh Ying Liao

Masters Theses & Specialist Projects

Water soluble platinum complexes are a recent area of emphasis of cisplatin chemistry. The water soluble complexes could have a reduced toxicity compared with cisplatin. Oxaliplatin, which has an oxalate leaving group, has previously been shown to have less nephro-toxicity and higher water solubility than cisplatin. [Pt(en)(oxalate)] (en = ethylenediamine) has been prepared from Pt(en)Cl2 and silver oxalate. This complex has been reacted with methionine and N-acetylmethionine at different molar ratios. At high Pt: methionine ratios, chelates with the sulfur and nitrogen atoms of the methionine are dominant; at lower Pt: methionine ratios, a bis-methionine product is ...


Nmr Resonance Assignment Of The Therapeutic Rna Aptamer Macugen In Complex With Its In Vivo Target, The Heparin Binding Domain Of Vegf165, Andrew Eric Libby Jan 2010

Nmr Resonance Assignment Of The Therapeutic Rna Aptamer Macugen In Complex With Its In Vivo Target, The Heparin Binding Domain Of Vegf165, Andrew Eric Libby

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

Aptamers consist of nucleic acids that are selected from an in vitro library in order to bind a specific target or catalyze a reaction. Many aptamer-ligand structures have been solved in recent years to characterize the molecular mechanisms that explain the high affinity and specificity observed in these interactions. To this end, NMR resonance assignment experiments were performed as a necessary first step to calculating the solution structure of a therapeutically-active RNA aptamer, Macugen, bound to its in vivo target, the heparin binding domain (HBD) of vascular endothelial growth factor 165 (VEGF165). Though the resonance assignment of Macugen is challenging ...


Targeting Base Excision Repair Suggests A New Therapeutic Strategy Of Fludarabine For The Treatment Of Chronic Lymphocytic Leukemia, A. D. Bulgar, M. Snell, J. R. Donze, E. B. Kirkland, Lan Li, Shuming Yang, Yan Xu, S. L. Gerson, Lili Liu Jan 2010

Targeting Base Excision Repair Suggests A New Therapeutic Strategy Of Fludarabine For The Treatment Of Chronic Lymphocytic Leukemia, A. D. Bulgar, M. Snell, J. R. Donze, E. B. Kirkland, Lan Li, Shuming Yang, Yan Xu, S. L. Gerson, Lili Liu

Chemistry Faculty Publications

No abstract provided.


Improved Arene Fluorination Methodology For I(Iii) Salts, Bijia Wang, Linlin Qin, Kiel D. Neumann, Shriharsha Uppaluri, Ronald Cerny, Stephen G. Dimagno Jan 2010

Improved Arene Fluorination Methodology For I(Iii) Salts, Bijia Wang, Linlin Qin, Kiel D. Neumann, Shriharsha Uppaluri, Ronald Cerny, Stephen G. Dimagno

Ronald Cerny Publications

The use of low polarity aromatic solvents (benzene or toluene) and/or the removal of inorganic salts results in dramatically improved yields of fluorinated arenes from diaryliodonium salts. This methodology is shown to “scale down” to the conditions used typically for radiotracer synthesis.


Solid Supported Synthesis Of Secondary Amines Via Staudinger And Microwave Aza-Wittig Reactions, Kyle Thomas Holsinger Jan 2010

Solid Supported Synthesis Of Secondary Amines Via Staudinger And Microwave Aza-Wittig Reactions, Kyle Thomas Holsinger

Undergraduate Honors Thesis Collection

Amine bond formation is a major topic in organic chemistry and is widely applied to the formation of medicinal compounds. Current studies have analyzed the benefits of microwave irradiation and solid supported reagents in order to improve reaction conditions and both synthetic and environmental costs. In the synthesis of amines, we investigate the combined use of microwave irradiation and solid supported reagents in the aza-Wittig and reductive amination reaction.


New 2-Aminoethylimidazole-Based Dicarboxylic Acid Receptor Derived From Cholestane, Jyoti Ramesh Jadhav, Md Wasi Ahmad, Hong Seok Kim Dec 2009

New 2-Aminoethylimidazole-Based Dicarboxylic Acid Receptor Derived From Cholestane, Jyoti Ramesh Jadhav, Md Wasi Ahmad, Hong Seok Kim

Dr. Mohammad Wasi Ahmad (Md Wasi Ahmad)

A new facial amphiphile cholestane-based receptor 1 containing a 2-imidazolylethylamino moiety at the 3a and 7a positions of cholestane was synthesized. Recognition selectivity of the new receptor 1 with various dicarboxylic acids was assessed by 1H NMR titration. Maleic acid showed the highest binding constant among all the tested acids