Medicinal Chemistry and Pharmaceutics Commons^™

Studies On Two Polyherbal Formulations (Zpto And Zto) For Comparison Of Their Antidyslipidemic, Antihypertensive And Endothelial Modulating Activities, Nauman Aziz, Malik Hassan Mehmood, Anwarul Hassan Gilani

Department of Biological & Biomedical Sciences

Background

Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs.

Methods

To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and …

Investigation Of The Structure And Dynamics Of Regioisomeric Eu³⁺ And Gd³⁺ Chelates Of Nb-Dotma: Implications For Mri Contrast Agent Design, Benjamin Charles Webber

Dissertations and Theses

The detection of disease and abnormal pathology by magnetic resonance imaging (MRI) has been aided significantly by the use of gadolinium (Gd³⁺)-based contrast agents (CAs) over the past three decades. MRI and MRI CAs play a critical role in diagnosing tumors and diseases of the central nervous system. The agents used clinically have been shown to safely increase MRI contrast despite the toxicity of Gd³⁺, owing to the high kinetic and thermodynamic stability of these chelates. However, current CAs enhance contrast at a small fraction of what is theoretically possible. This leads to the necessity of …

Cytochrome P450 Family 1 Inhibitors And Structure-Activity Relationships, Jiawang Liu, Jayalakshmi Sridhar, Maryam Foroozesh

Faculty and Staff Publications

With the widespread use of O-alkoxyresorufin dealkylation assays since the 1990s, thousands of inhibitors of cytochrome P450 family 1 enzymes (P450s 1A1, 1A2, and 1B1) have been identified and studied. Generally, planar polycyclic molecules such as polycyclic aromatic hydrocarbons, stilbenoids, and flavonoids are considered to potentially be effective inhibitors of these enzymes, however, the details of the structure-activity relationships and selectivity of these inhibitors are still ambiguous. In this review, we thoroughly discuss the selectivity of many representative P450 family 1 inhibitors reported in the past 20 years through a meta-analysis.

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations and Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with ^99mTc and ⁶⁸Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both ^99mTc-N4amG and ^99mTc-GP were stable up to 6 hours, whereas ⁶⁸Ga-GP was stable up to 2 hours. Cell culture studies …

Mechanisms Of Cytokine-Induced Metabolic Dysfunction Of The Pancreatic Beta-Cell, Abiy Mussa Mohammed

Wayne State University Dissertations

MECHANISMS OF CYTOKINE-INDUCED METABOLIC DYSFUNCTION OF THE PANCREATIC BETA-CELL

by

ABIY MUSSA MOHAMMED

August 2013

Advisor: Dr. Anjaneyulu Kowluru

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Type I diabetes is characterized by an absolute insulin deficiency due to loss of pancreatic â-cell mass by autoimmune aggression. During the progression of the disease proinflammatory cytokines such as IL-1â, TNFá and INFã are secreted by infiltrated and activated T-cells and macrophages which ultimately damage the pancreatic â-cell. However, the signaling mechanisms involved in cytokine-induced damage are only partially understood. Phagocyte-like NADPH oxidase [NOX2] has been shown to play regulatory roles in the …

Polymeric Nanocarriers And Their Oral Inhalation Formulations For The Regional Delivery Of Nucleic Acids To The Lungs, Denise Santos Conti

Wayne State University Dissertations

Gene therapy has attracted attention in the fields of medicine, pharmacy, and bionanotechnology due to the potential for treating a large number of medically relevant diseases. Oral inhalation (OI) is a promising route for the administration of therapeutics, including small molecules and biomacromolecules, such as nucleotides, peptides, and proteins, to (locally) and through (systemically) the lungs. The use of OI is especially attractive for the delivery of nucleic acids as it provides a direct and non-invasive route for targeting the lungs. Pressurized metered-dose inhalers (pMDIs), are the most commonly used OI in treatment of lung diseases and are thus promising …

Chlomid, Niki Smith

Natural Sciences Student Research Presentations

This poster details the use of Clomid and provides a chemical analysis.

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …

Cure From The Cave: Volcanic Cave Actinomycetes And Their Potential In Drug Discovery, Naowarat (Ann) Cheeptham Dr., Tara Sadoway, Devon Rule, Kent Watson, Paul Moote, Laiel C. Soliman, Nicholas Azad, Kingsley Donkor, Derrick Horne

International Journal of Speleology

Volcanic caves have been little studied for their potential as sources of novel microbial species and bioactive compounds with new scaffolds. We present the first study of volcanic cave microbiology from Canada and suggest that this habitat has great potential for the isolation of novel bioactive substances. Sample locations were plot ted on a contour map that was compiled in ArcView 3.2. Over 400 bacterial isolates were obtained from the Helmcken Falls cave in Wells Gray Provincial Park, British Columbia. From our preliminary screen, of 400 isolates tested, 1% showed activity against extended spectrum ß-lactamase E. coli, 1.75% against Escherichia …

Oligospermines For Non-Viral Sirna Delivery, Maha Elsayed

Wayne State University Theses

In this thesis, delivery systems for siRNA delivery are introduced with special attention to non-viral vectors. Many successful vectors used in vivo were reviewed. Our work focused on the effect of different architectures of oligospermine polmers on their suitability for siRNA delivery in lung cancer cells. Different archituctures showed different polyplex structures and variable transfection efficiencies. Moreover, we presented a review on nanoimprint lithography techniques with an outlook on possible biological applications in the field of gene and drug delivery.

The Antiinflammatory Action And Pharmacokinetics Of A Novel Glucosamine-Based Di-Peptide Aminosugar, Mohammad H. Gilzad-Kohan, Kamaljit Kaur, Fakhreddin Jamali

Pharmacy Faculty Articles and Research

Purpose. We have previously shown favorable in vitro gut permeability for three novel dipeptide esters of glucosamine (GlcN) likely facilitated by the peptide transporter 1 (PepT1). Herein, we report the development of a novel assay for the determination of bioavailability of the peptide ester of interest, the anti-inflammatory properties of a glycine-valine ester derivative of GlcN (GVG) as well as its pharmacokinetics under healthy and inflammatory conditions.

Methods. A pre-column derivatization (with 9-fluorenylmethoxycarbonyl) HPLC assay was developed to study bioavailability of GVG, GlcN or cleaved GlcN in the rats that were cannulated in their right jugular vein for …

Synthesis And Biochemical Activities Of Antiproliferative Amino Acid And Phosphate Derivatives Of Microtubule-Disrupting Beta-Lactam Combretastatins, Niamh M. O'Boyle, Lisa M. Greene, Niall O. Keely, Shu Wang, Tadhg S. Cotter, Daniela M. Zisterer, Mary J. Meegan

Articles

The synthesis and biochemical activities of novel water-soluble β-lactam analogues of combretastatin A-4 are described. The first series of compounds investigated, β-lactam phosphate esters 7a, 8a and 9a, exhibited potent antiproliferative activity and caused microtubule disruption in human breast carcinoma-derived MCF-7 cells. They did not inhibit tubulin polymerisation in vitro, indicating that biotransformation was necessary for their antiproliferative and tubulin binding effects in MCF-7 cells. The second series of compounds, β-lactam amino acid amides (including 10k and 11l) displayed potent antiproliferative activity in MCF-7 cells, disrupted microtubules in MCF-7 cells and also inhibited the polymerisation of …

Novel Cis-Restricted Β-Lactam Combretastatin A-4 Analogues Display Anti-Vascular And Anti-Metastatic Properties In Vitro, Seema M. Nathwani, Lisa M. Greene, Linda Hughes, Miriam Carr, Niamh O'Boyle, Susan Mcdonnell, Mary J. Meegan, Daniela M. Zisterer

Articles

No abstract provided.

Formulation Devlopment Of Mesoporous Silica Nanoparticles As An Injectable Delivery System, Amit S. Wani

Wayne State University Dissertations

Our long term goal is to develop a versatile and robust injectable carrier based on Mesoporous Silica Nanoparticles (MSN) for drug/drug combination therapies. The objective of my dissertation was to optimize surface functionality, particle shape and methods of colloidal stabilization of mesoporous silica by PEG for delivery of drug/drug combinations. This was achieved by pursuing the following three aims:

1. Optimize surface functionality of MSN for high drug loading and controlled release

2. Investigate the effect of particle shape and PEGylation on drug delivery in hypoxic tumor cells

3. Develop MSN capable of delivering drug/drug combinations

To investigate the effect …

Progress Towards Development Of Multifunctional, Dopamine D2/D3 Receptor Agonists As Symptomatic And Disease-Modifying Therapeutic Agents For Parkinson's Disease, Mark Andrew Johnson

Wayne State University Dissertations

Parkinson¡¯s disease (PD) is a progressive, neurodegenerative disorder that arises primarily through the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), resulting in a diminished level of the neurotransmitter dopamine in the nigrostriatal pathway and ensuing loss of motor function. Common symptoms of PD include resting tremor, muscular rigidity, bradykinesia (slowness and decreased amplitude of movement), along with postural instability and cognitive psychiatric complications. PD affects 1% of the population ¡Ý 65 and is the second most prevalent neurodegenerative disorder next to Alzheimer¡¯s disease (AD). Although the etiology of PD is not yet clear and may be …

Progress Towards Understanding Of Mechanisms Of Action Of Potent Multifunctional Disease Modifying Therapeutics For Parkinson's Disease & Investigating The Methamphetamine-Induced Striatal Microglia Activation., Mrudang M. Shah

Wayne State University Dissertations

PROGRESS TOWARDS UNDERSTANDING OF MECHANISMS OF ACTION OF POTENT MULTIFUNCTIONAL DISEASE MODIFYING

THERAPEUTICS FOR PARKINSON'S DISEASE.

by

MRUDANG MANOJKUMAR SHAH

December 2013

Advisor: Dr. Aloke Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Our long term goal is to design and develop potent multifunctional disease modifying therapeutics for Parkinson's disease. The objective of my dissertation was to understand the mechanisms of action of some potent small molecules (synthesized in our lab) as a disease modifying Parkinson's disease therapeutic. The objective was achieved by pursuing the following two specific aims:

1. Investigating anti-oxidant and neuroprotective effects of a lead molecule (D-512) …

Design, Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Multifunctional Neuroprotective Drugs For The Treatment Of Parkinson's Disease: An Effort Towards The Improvement Of In Vivo Efficacy And Modulation Of Alpha Synuclein Aggregation Property Of The Neuroprotective Parent, Gyan Prakash Modi

Wayne State University Dissertations

DESIGN, SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR MODELING STUDIES OF NOVEL MULTIFUNCTIONAL NEUROPROTECTIVE DRUGS FOR THE TREATMENT OF PARKINSON'S DISEASE: AN EFFORT TOWARDS THE IMPROVEMENT OF IN VIVO EFFICACY AND MODULATION OF ALPHA SYNUCLEIN AGGREGATION PROPERTY OF THE NEUROPROTECTIVE PARENT MOLECULE (D-264)

by

GYAN PRAKASH MODI

May 2014

Advisor: Dr. Aloke K. Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Parkinson's disease (PD) is a progressive age-related neurodegenerative disorder of the central nervous system that is characterized by gradual loss of dopaminergic neurons in the substantia nigra region of the brain. The research from the past two decades in PD area …