Medicinal Chemistry and Pharmaceutics Commons^™

Human Ecology, Spring/Summer 2016, Issue 34

Sustain Magazine

No abstract provided.

Citizen Science, Fall/Winter 2016, Issue 33

Sustain Magazine

No abstract provided.

Urban Streams, Spring/Summer 2015, Issue 32

Sustain Magazine

No abstract provided.

Unconventional Energy, Fall/Winter 2015, Issue 31

Sustain Magazine

No abstract provided.

Carbon Neutral, Spring/Summer 2018, Issue 38

Sustain Magazine

No abstract provided.

Political Will, Fall/Winter 2018, Issue 37

Sustain Magazine

No abstract provided.

Our Envirome, Spring/Summer 2019, Issue 40

Sustain Magazine

No abstract provided.

Plastic Pollution, Fall/Winter 2019, Issue 39.3

Sustain Magazine

No abstract provided.

Plastic Pollution, Fall/Winter 2019, Issue 39.2

Sustain Magazine

No abstract provided.

Plastic Pollution, Fall/Winter 2019, Issue 39

Sustain Magazine

No abstract provided.

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of …

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Pbrm1 Regulates Stress Response In Epithelial Cells, Elizabeth G. Porter, Alisha Dhiman, Basudev Chowdhury, Benjamin C. Carter, Hang Lin, Jane C. Stewart, Majid Kazemian, Michael K. Wendt, Emily C. Dykhuizen

Department of Biochemistry Faculty Publications

Polybromo1 (PBRM1) is a chromatin remodeler subunit highly mutated in cancer, particularly clear cell renal carcinoma. PBRM1 is a member of the SWI/SNF subcomplex, PBAF (PBRM1-Brg1/Brm-associated factors), and is characterized by six tandem bromodomains. Here we establish a role for PBRM1 in epithelial cell maintenance through the expression of genes involved in cell adhesion, metabolism, stress response, and apoptosis. In support of a general role for PBRM1 in stress response and apoptosis, we observe that loss of PBRM1 results in an increase in reactive oxygen species generation and a decrease in cellular viability under stress conditions. We find that loss …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

Development Of Mithramycin Analogues With Improved Efficacy And Reduced Toxicity For Treatment Of Ets-Dependent Tumors In Ewing Sarcoma And Prostate Cancer, Joseph Michael Eckenrode

Theses and Dissertations--Pharmacy

Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor …

Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction, Ahmed Hamish Neamah Al-Darraji

Theses and Dissertations--Pharmacology and Nutritional Sciences

Introduction: Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Induced by cardiomyocyte death, MI initiates a prolonged and uncontrolled inflammatory response which impairs the healing process. Immune cells, such as macrophages, play a central role in organizing the early post-MI inflammatory response and the subsequent repair phase. Two activation states of macrophages have been identified with distinct and complementary functions (inflammatory vs. reparatory). This bimodal pattern of macrophage activation is an attractive therapeutic target to favorably resolve post-MI inflammation and enhance recovery. It has been demonstrated that azithromycin (AZM), a commonly used antibiotic with immunomodulatory effects, …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations and Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

The Pharmaceutical Industry: A Pharmacy Student's Guide, Christian Egly, Yaman Kaakeh

Purdue Journal of Service-Learning and International Engagement

Christian Egly is a fourth-year (P4) pharmacy student in the Purdue University College of Pharmacy. During his years at Purdue, he worked in labs performing bench research in clinical pharmacology and biochemistry. He plans to work in the pharmaceutical industry after graduation. During his fourth year, he completed rotations in business development at Kashiv Pharma, LLC, and was hired there for an internship in 2017. In the article, Christian describes his personal experiences at Kashiv Pharma, LLC, and how industry can positively affect patient communities.

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Structure Based Drug Design Of High Affinity Kras Inhibitors, Michael Mccarthy

Dissertations and Theses (Open Access)

RAS, one of the most well characterized membrane-associated small GTPases, is a notorious oncogene with >15% of all tumors harboring RAS mutations. When RAS is mutated it becomes constitutively active sending cell growth, survival and proliferation into overdrive, which subsequently leads to cancer. Although, RAS has been aggressively targeted with drug design efforts for more than 30 years an FDA approved direct inhibitor has not yet been developed. There are three isoforms of RAS in cells; HRAS, NRAS and KRAS. We focused on KRAS since it is the most frequently mutated isoform in cancer. To identify novel non-covalent small molecules …

The Combined Neuropharmacology And Toxicology Of Major 'Bath Salts' Constituents Mdpv, Mephedrone, And Methylone, Serena Allen

Electronic Theses and Dissertations

The synthetic cathinones, 3,4- methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4- methylenedioxymethcathinone (methylone), gained worldwide notoriety as the psychoactive components of ‘bath salts;’ a marketing term used to circumvent federal drug laws and permit their legal sale. Previous studies have shown that these drugs share pharmacological characteristics with cocaine and the amphetamines, however, descriptions of their neurotoxic properties are limited. Moreover, while forensic analysis has revealed that the most frequently abused bath salts ‘brands’ contain binary and ternary mixtures of MDPV, mephedrone, and methylone, the majority of preclinical research has focused on explicating the individual effects of these drugs. Therefore, the …

Evaluating The Aryl Hydrocarbon Receptor As A Target For Pharmacologic Activity Of Repurposed Drugs, Teofilo Borunda Duque

Pharmaceutical Sciences ETDs

The discovery of new pharmacologic targets is important for the advancement of pharmacotherapy and identification of new indications for current drugs. The aryl hydrocarbon receptor (AHR) is a physiologic sensor of both chemical environmental pollutants and ligands of natural origin. Given the broad spectrum of ligands that activate the AHR and its relationship with toxicology, the AHR is not thought to be a traditional target for pharmacotherapy. However, multiple studies have shown potential for the AHR as a novel pharmacologic target Therefore, identifying less toxic agents that modulate the AHR may elucidate mechanisms for pharmacological targeting of the AHR. The …

Discovery And Effects Of Pharmacological Inhibition Of The E3 Ligase Skp2 By Small Molecule Protein-Protein Interaction Disruptors, John K. Morrow

Dissertations and Theses (Open Access)

Skp2 (S-phase kinase-associated protein 2), one component of the SCF E3 ubiquitin ligase complex, directly interacts with Skp1 and indirectly associates with Cullin1 and Rbx1 to bridge the E2 conjugating enzyme with its protein substrate to execute its E3 ligase activity. Skp2 is an Fbox protein (due to it containing an Fbox domain) and it is the rate-limiting component of the SCF complex. Skp2 targets several cell-cycle regulatory proteins for ubiquitination and degradation; most notable and significant for cancer are the cyclin-dependent kinase inhibitor, p27. Skp2 is an oncogene and studies have shown that over-expression of Skp2 leads to increased …

The Development Of Novel Non-Peptide Proteasome Inhibitors For The Treatment Of Solid Tumors, Zachary C. Miller

Theses and Dissertations--Pharmacy

The proteasome is a large protein complex which is responsible for the majority of protein degradation in eukaryotes. Following FDA approval of the first proteasome inhibitor bortezomib for the treatment of multiple myeloma (MM) in 2003, there has been an increasing awareness of the significant therapeutic potential of proteasome inhibitors in the treatment of cancer. As of 2017, three proteasome inhibitors are approved for the treatment of MM but in clinical trials with patients bearing solid tumors these existing proteasome inhibitors have demonstrated poor results. Notably, all three FDA-approved proteasome inhibitors rely on the combination a peptide backbone and reactive …

The Forensic Characterization Of Bacterial And Fungal Organisms In Traditional Chinese Medicine, Julia Grzymkowski, Christopher J. Ehrhardt, Justin L. Poklis, Michelle R. Peace

Undergraduate Research Posters

There has been an increase in use of Traditional Chinese Medicine (TCM) in the United States because they are less expensive and believed to be more effective with less adverse effects in comparison to traditional pharmaceutics. Therefore, sales have increased in the US, despite articles and case studies demonstrating the dangers, such as injury and death, related to TCM, stemming from improper labelling, toxic contaminants, and, in some cases, the presence of pathogenic bacteria. The aim of this study was to perform a survival experiment to demonstrate the importance of proper herbal brewing technique and to conduct a molecular and …

In Silico Study Of Newly Synthesized Opioid Analgesics Bound To Three Opioid Receptors, Abdullah Allaoa, Mai Zahran

Publications and Research

Opioids are the most widely used drugs for the treatment of moderate to severe, chronic pain. They achieve antinociception by activation of mu (MOR-1), kappa (KOR-1), and delta (DOR-1) opioid receptors. Natural products found in kratom plant, Mitragyna speciosa, represent diverse chemical groups with opioid activity, providing opportunities to better understand opioid pharmacology. Pharmacology studies show that Mitragynine pseudoindoxyl is a mu agonist/delta antagonist opioid with a signaling bias for G-protein-mediated signaling pathways in vitro and which produced potent antinociception in vivo. Respiratory depression assays along with other behavioral testing also showed that some of the major problems …

Phytochemical Screening And Determination Of Antibacterial, Anti-Tumorigenic And Dna Protection Ability Of Root Extracts Of Saussurea Lappa, Sughra Arif Minhas, Fida Muhammad Khan, Fakhar-I- Abbas, Abu Ul Hassan Faiz

Journal of Bioresource Management

Saussurea lappa is a traditionally well-known plant for its medicinal uses in different indigenous systems of medicine. It is widely used in the treatment of asthma, ulcer, stomach problems and inflammatory diseases. In current study the phytochemical screening of S. lappa showed the presence of sesquiterpenes, anthraquinones, lignans, alkaloids, flavonoids, glycosides and steroids. Antimicrobial potential of subject plant was also investigated against three bacterial strains and maximum antibacterial activity was observed by CEE against S. aureus, CAE against P. aeruginosa, while CME, CEE, EAE and PEE showed almost same significant activity against E. coli. The CME (1000 …

Rxtx And Micromedex, Shawn Hendrikx, Kelly Hatch

Western Libraries Publications

No abstract provided.

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …