Medicinal and Pharmaceutical Chemistry Commons^™

Effects Of Sex And Estrous Cycle On Extended-Access Oxycodone Self-Administration And Cue-Induced Drug Seeking Behavior, Bhumiben P Patel, Jessica A Loweth

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Increasing evidence indicates that sex is a factor that impacts the abuse liability and relapse vulnerability of prescription opioids like oxycodone. However, while women are more likely than men to be prescribed and to use these drugs, the impact of sex and ovarian hormones on prescription opioid use and relapse vulnerability remains unclear. Accurately assessing these measures is complicated by the fact that chronic opioid exposure can lower ovarian hormone levels and cause cycle irregularities.

METHODS: Adult male and female Sprague-Dawley rats self-administered oxycodone (0.1 mg/kg/infusion) under extended-access conditions (6 h/day, 10 days) followed by forced abstinence. Separate groups …

Potent And Selective Small Molecule Mcl-1 Inhibitor Demonstrates Anti-Myeloma Activity And Overcomes Chemotherapy Resistance, Omar Sami Faleh Al-Odat

Theses and Dissertations

Despite a record number of clinical studies investigating various anti-myeloma treatments, the 5-year survival rate for multiple myeloma (MM) patients in the US is only 55%, and nearly all patients relapse. Poor patient outcomes demonstrate that myeloma cells are "born to survive” which means they can adapt and evolve following treatment. Thus, new therapeutic approaches to combat survival mechanisms and target treatment resistance are required. Importantly, Mcl-1, anti-apoptotic protein, is required for the development of MM and treatment resistance. This study looks at the possibility of KS18, a selective Mcl-1 inhibitor, to treat MM and overcome resistance. Our investigation demonstrates …

An Integrative Review Of The Absorption Of Fda-Approved Chemical Sunscreen Filters Into The Blood, Srinidhi Banala, Samrat Gollapudi, Abhiram Gollapudi, Bhaumik Patel

Rowan-Virtua Research Day

Introduction: This integrative review examines the absorption of FDA-approved chemical sunscreen filters, specifically avobenzone and oxybenzone, into the bloodstream. The study aims to compare the levels of absorption and potential health effects of systemic exposure to these sunscreen ingredients in the United States.

Methods: The researchers conducted a literature search of 57 articles, of which 15 were used for the review. Inclusion criteria focused on studies discussing absorption levels of avobenzone and oxybenzone, as well as methods of absorption into the bloodstream. Exclusion criteria included sunscreen ingredients not approved in the United States, non-English studies, and studies on methods to …

Behavioral Effects Of Novel Treatments For Pain Using Different Pathways, Danya M I Aldaghma

Theses and Dissertations

Pain is defined as an unpleasant sensation that is mostly caused by a stimulus from our surroundings. This sensation has the potential to become a significant concern, disrupting daily activities, and diminishing overall quality of life. However, it could also hold significant importance as it serves as a protective mechanism. Pain acts as an alarm system for the human body, alerting it to potentially harmful situations where tissues may be at risk of damage1. Despite the considerable advancements in pain treatment and the extensive knowledge scientists possess regarding the pathophysiology and pathways of pain, numerous medications aimed at alleviating pain …

Probing The Activation Mechanisms Of Agonist Dpi-287 To Delta-Opioid Receptor And Novel Agonists Using Ensemble-Based Virtual Screening With Molecular Dynamics Simulations., Emily Dean, Annemarie Dominique, Americus Palillero, Annie Tran, Nicholas Paradis, Chun Wu

College of Science & Mathematics Departmental Research

Pain drugs targeting mu-opioid receptors face major addiction problems that have caused an epidemic. The delta-opioid receptor (DOR) has shown to not cause addictive effects when bound to an agonist. While the active conformation of the DOR in complex with agonist DPI-287 has been recently solved, there are still no FDA-approved agonists targeting it, providing the opportunity for structure-based virtual screening. In this study, the conformational plasticity of the DOR was probed using molecular dynamics (MD) simulations, identifying two representative conformations from clustering analysis. The two MD conformations as well as the crystal conformation of DOR were used to screen …

Computational Study Of Foldamer-Based Water Channels, Shadi Houshyar Azar

Theses and Dissertations

One of the most serious global challenges of this century is water scarcity, stemming primarily from the growing demand for freshwater and the depletion of freshwater resources. Water desalination has the potential to address this problem, but current technologies are expensive and inadequate. Here, we present novel, computationally designed channels with high water permeability and selectivity against ions, inspired by natural water channels, aquaporins. Aquaporin's unique property of transporting water while rejecting protons and other ions has led to numerous studies on incorporating such channels into different membranes for water purification applications. However, use of an aquaporin-incorporated membrane is limited …

Isolated Temazepam Overdose: A Unique Case Of An Unresponsive Female, Eric Doane

Rowan-Virtua Research Day

Cases of acute overdose presenting to the emergency department pose a great challenge given that history can sometimes be limited or at times be inaccurate. While naloxone is routinely given in the field to help reduce opiate’s sedating effects, the routine use of flumazenil has not been routinely adopted in cases of benzodiazepine overdose. This is because, unlike naloxone, there are many medications that act on the GABA receptor, and flumazenil is only specific for binding to the benzodiazepine/GABA receptor. This can lead to an unmasking of other medications that may be co-ingested that also effect the GABA receptor leading …

Debunking Old Evolution Theories, Proposing New One (Near Neutral Balanced Selection Theory/Nnbst) Using Sars Cov 2 Genomic Data, Chun Wu

College of Science & Mathematics Departmental Research

The COVID 19 pandemic has caused 672 million infections and 6 million deaths understanding the molecular evolution of this virus is critical to ending this pandemic • The SARS CoV 2 genome exhibits a time independent, constant genomic substitution rate ( despite increasing vaccinations and infected human cases (Figure 1 A) • Out of the three main evolutionary theories S electionist Theory/ST, Kimura’s Neutral Theory/KNT, Ohta’s Nearly Neutral Theory/ONNT), the SARS CoV 2 GSR seemingly follows KNT but this does not explain the critical intervention by vaccines and therapeutic drugs on the evolution of this virus I n this study …

Antiviral Drug Development: Targeted Design And Broad Spectrum Approach, Claude Krummenacher

College of Science & Mathematics Departmental Research

No abstract provided.

Fabrication And Comparative Study Of Horizontal And Vertical Electrospun Protein-Polysaccharide Nanofiber Biomaterials, Ashley Rivera-Galleti

Theses and Dissertations

The use of biocompatible and biodegradable composite materials for biomedical applications has attracted the attention of many researchers in the past few years. In this study, we fabricated nanofibers of silk fibroin and cellulose and its derivatives to amalgamate their unique properties into a single material. The production of these nanofibers via electrospinning is of particular interest, and whereas several studies have been done on normal nanofibers, the formation of branched nanofibers is an exciting area not currently explored. Blend solutions are formed by dissolving silk and cellulose/cellulose acetate in formic acid separately and mixing to achieve the desired ratios. …

Investigation Of The Role Of Hydrophobic Amino Acids On The Structure-Activity Relationship In Ponericin L1 From Neoponera Goeldii, Nicholas Patrick Schifano

Theses and Dissertations

Due to the increase prevalence of antimicrobial resistance (AMR) antibiotic alternatives have been of great interest. Antimicrobial peptides (AMPs) and polymers like polymethacrylates that mimic AMPs are two non-traditional antimicrobial agents that have been investigated thoroughly over the years as a potential solution to the AMR problem. This study will further the understanding of the L1 peptide by investigating the role hydrophobic amino acids have on the antimicrobial activity. Biophysical and microbiological techniques were utilized to show that the L1 hydrophobic derivative showed enhanced binding to anionic lipid bilayers while maintaining low hemolytic activity. This study also elucidates the effect …

Endeavors Toward Novel Synthetic Roadmaps In The Synthesis Of Pertinent Pharmacological Molecular Scaffold Moieties, Justin David Horgan

Theses and Dissertations

One of the main goals in the GML lab group is the development of novel, economical, and environmentally friendly organic methods for the synthesis of pharmacologically relevant molecular moieties. The most salient pieces of data to the GML lab group members, reading dependable organic journals, are finding organic moieties that are largely unexplored, finding organic moieties which various research groups are having difficulty synthesizing, and finding complex organic procedures to key organic structures that can be easily reduced, or reconstructed, into novel methods that are more economical and environmentally friendly. By looking at these unexplored molecules, as well as hard …

The Exploration Of Novel Synthetic Methods Of Biologically Relevant Nitrogen And Halogen Containing Molecules, Rebekah Erin Strong

Theses and Dissertations

Visible light has become a highly useful, and regarded, tool to the organic chemist. The additions and transformations of an abundance of molecules can be achieved with the use of visible light and photocatalysts, when appropriate. More specifically compounds that contain nitrogen, halogens, or both are highly useful structures in nearly every chemical industry. They are elements found in naturally occurring molecules and have the capacity to mimic biologically active and relevant structures. This makes them useful targets for pharmaceutical compounds. Bromine and chlorine can act as leaving groups; this property makes molecules with these elements reactive and thus able …

Mcl-1 Inhibition: Managing Malignancy In Multiple Myeloma., Omar Al-Odat, Max Von Suskil, Robert Chitren, Weam Elbezanti, Sandeep Srivastava, Tulin Budak-Alpddogan, Subash C. Jonnalagadda, Bharat Aggarwal, Manoj Pandey

College of Science & Mathematics Departmental Research

Multiple myeloma (MM) is a plasma cells neoplasm. The overexpression of Bcl-2 family proteins, particularly myeloid cell leukemia 1 (Mcl-1), plays a critical role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with drug resistance and overall poor prognosis of MM. Thus, inhibition of the Mcl-1 protein considered as a therapeutic strategy to kill the myeloma cells. Over the last decade, the development of selective Mcl-1 inhibitors has seen remarkable advancement. This review presents the critical role of Mcl-1 in the progression of MM, the most prominent BH3 mimetic and semi-BH3 mimetic that selectively inhibit Mcl-1, and …

Computational Study Of Drug Interactions Of Receptors, Specifically Glycoprotein D Of Human Herpes Virus 1 And Dopamine D4 Receptor, Griffin Fountain

Theses and Dissertations

This thesis introduces computer-aided drug design methods in Chapter 1 and discuss their applications on two receptors in Chapters 2 and 3: Glycoprotein D (gD) of Herpes Simplex Virus 1 (HSV-1) and Dopamine Receptor D4 (DRD4). The Herpes Simplex Virus is a human pathogen that develops unpleasant cold sores around the body, most commonly around the mouth, neck or genitals area. Currently there is no cure or vaccine that can eliminate this virus. Glycoprotein D (gD) is a viral ligand for host cell receptors such as nectin -1. This interaction mediates the entry of HSV-1. In chapter 2, we used …

Behavioral Analysis Of Conditions And Treatments Affecting Movement And Nociception, Indu Mithra Madhuranthakam

Theses and Dissertations

This thesis work includes three projects. First part deals with the investigation of novel D2 receptor ligands in Prepulse inhibition. The goal of this study is to establish a relationship between dopamine receptor antagonists and agonists and prepulse inhibition which can then serve as a working model for an in-vivo efficacy of novel dopamine D2 drugs. The second part of the thesis work deals with Niemann pick disease type C. Niemann pick disease type C is a progressive genetic disorder that is characterized by the lysosomal accumulation of lipids which causes neurodegeneration, dementia, ataxia, and death. NPC1_nmf164 mutant mice …

Efforts Toward Novel Methods For The Synthesis Of Stereochemically-Dense Pharmacologically Relevant Scaffolds, Lauren Nicole Tumbelty

Theses and Dissertations

Nitrogen is the most common pure element, present in nearly all relevant chemical compounds. It is an essential component of the building blocks of life such as proteins, nucleic acids, amino acids and adenosine tri-phosphate. There is a naturally occurring exchange between living organisms and the atmosphere which begins with the process of fixation. Although nitrogen is naturally abundant, the strength of the triple bond in atmospheric nitrogen prevents its applicability in organic synthesis. Therefore, the development of methods to place synthetic nitrogen into heteroatomic compounds plays an important role in the development of pharmacologically relevant scaffolds. Contained within this …

Lipoxin A 4 (Lxa 4 ) Promotes Reduction And Antibiotic Efficacy Against Pseudomonas Aeruginosa Biofilm, Julianne M. Thornton, Jean Walker, Prem Yugandhar Kadiyam Sundarasivarao, Bernd Spur, Ana Rodriguez, Kingsley Yin

Rowan-Virtua Research Day

Pseudomonas aeruginosa (P aeruginosa) is an opportunistic bacterium commonly found in wound infections and airways of cystic fibrosis patients P aeruginosa readily forms biofilms which can reduce the efficacy of antibiotics used to eradicate the pathogen We have previously shown that a Specialized Pro resolving Mediator ( Lipoxin A 4 (LxA 4 is a quorum sensing inhibitor which can reduce P aeruginosa virulence In this study, we examined the direct actions of LxA 4 and RvD 2 on P aeruginosa biofilm formation and virulence gene expression The influence of LxA 4 on antibiotic efficacy and the combined effects on biofilm …

Synergistic Interactions Of Ionic Liquids And Antimicrobials Improve Drug Efficacy., Daniel D Yang, Nicholas J Paterna, Alexandria S Senetra, Kaitlyn R Casey, Phillip D Trieu, Gregory A. Caputo, Timothy Vaden, Benjamin Carone

College of Science & Mathematics Departmental Research

Combinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and …

Investigation Of The Sequence-Structure-Activity Relationship In Ponericin L1 From Neoponera Goeldii & Synergistic Interactions Of Ionic Liquids And Antimicrobials To Improve Efficacy, Alexandria S. Senetra

Theses and Dissertations

Non-traditional antimicrobials have been an area of great interest due to the increasing prevalence of antimicrobial resistance (AMR) in bacteria. Antimicrobial peptides (AMPs) & ionic liquids (ILs) are two examples that have been investigated as a potential solution. Most AMPs are naturally derived & exhibit high selectivity against bacterial targets over host cells. The venom-derived peptide, ponericin L1 from Neoponera goeldii, was used to investigate the role of cationic residues & net charge on peptide activity. Using both in vitro & microbiological methods, L1 peptide & derivatives exhibited an alpha-helical conformation with enhanced binding to lipid vesicles containing anionic lipids …

Searching For New Medications For The Treatment Of Alcohol Use Disorder, Harley M. Buechler

Theses and Dissertations

Alcohol use disorder (AUD) affects more than 15 million people in the United States. Current pharmacotherapeutic treatments for AUD are only modestly effective, necessitating the identification of new targets for medications development. In this study, the effects of the D4 receptor antagonist, L-745,870, and the CB1 negative allosteric modulator, PSNCBAM-1, were both tested for effects in ethanol conditioned place preference (CPP) and oral ethanol self-administration. Food-restricted adult male mice were trained in operant chambers to nose poke for delivery of rewards, trained on ascending concentrations of alcohol with descending concentrations of Ensure and water, until the mixture self-administered was 8% …

Searching For New Analgesics Without Addiction Risks, Mohammad Atiqur Rahman

Theses and Dissertations

Opioids are widely used to treat acute and chronic pain. But opioid addiction to these compounds can cause social and life-threatening health problems, including the risk of overdose. In this thesis, I evaluated IBNtxA (3-iodobenzoyl naltrexamine), a novel mu opioid receptor (MOR) agonist structurally related to the classical MOR antagonist naltrexone, in drug discrimination studies in order to better understand its subjective effects and more thoroughly its abuse liability. IBNtxA represents an intriguing lead compound for preclinical drug development specifically targeting MOR splice variants, potentially creating effective analgesics with reduced side effects. These results indicate that IBNtxA produces potent antinociception …

Synthesizing Modified Polymeric Nanoparticles For Biofilm Inhibition, Antibiotic Encapsulation, And Specific Targeting Against Pseudomonas Aeruginosa, Logan Schnorbus

Theses and Dissertations

Widespread usage of antibiotics is a growing concern due to antibiotic resistance development in bacteria. This is due to common use of antibiotics in agricultural, livestock, and clinical usage. Antibiotic resistance is developing at a rate in which it is outpacing new drugs on the market. New strategies in drug development are necessary to combat the increasing resistance. We designed several motifs of sugar-modified nanoparticles to inhibit the biofilm formation of Pseudomonas aeruginosa.

P. aeruginosa is an opportunistic pathogenic bacterium that is responsible for common life-threatening infection in hospitals. This gram-negative opportunistic pathogenic bacterium infects hosts with compromised immune systems …

An In Silico Study Of Small Molecule Anti-Cancer Agents Targeting Dna G-Quadruplexes, Holli-Joi Sullivan

Theses and Dissertations

Free ligand binding molecular dynamic simulations are a powerful tool used to probe the ligand binding process, mechanism and pathway and the insight gained can help expedite the early stages of drug discovery. Using these methods, we model the binding of two small molecule anti-cancer agents BRACO19 and CX-5461 to a variety of DNA G-quadruplexes (G4s) and a DNA Duplex. The first study focuses on the binding of BRACO19 to three different topological folds (parallel, anti-parallel and hybrid) of the human telomeric G4s. Our detailed analysis identified the most stable binding modes were end stacking and groove binding for the …

Synthesizing Galactose Modified Polymeric Nanoparticles For Biofilm Inhibition Of Pseudomonas Aeruginosa, Tyler R. Flockton

Theses and Dissertations

Treating patients with antibiotics is becoming harder with the increase in antibiotic resistance. This is due to the widespread antibiotic use in clinical and agricultural settings. With antibiotic resistance outpacing new drugs making it to the market, developing new options to treat bacterial infections is and will be important. We created sugar modified nanoparticles to inhibit the biofilm formation of Pseudomonas aeruginosa.

P. aeruginosa is a gram-negative opportunistic pathogen that infects its host that has a compromised immune system. This makes it one of the most significant bacterial infection in hospitals. P. aeruginosa uses biofilms as an attack mechanism …

Synthesis Of Betulinic Acid Via Baylis-Hillman Reaction, Sai Krishna Kommineni

Theses and Dissertations

Betulin is readily isolated from the bark of birch trees using simple extraction techniques and this molecule as well as its derivatives (eg. betulinic acid) exhibit impressive levels of biological activity. While it is naturally available and shows selective toxicity towards certain cancers, betulin suffers from a general lack of solubility in aqueous conditions. In this regard, we took up a project involving the synthesis of conjugates of betulin with improved solubility characteristics and we were able to identify a series of compounds that showed cytotoxicity against breast and pancreatic cancer cells.

This thesis describes our efforts on the development …

Development Of Functionalized Imidazoles As Potential Therapeutical Agents, Drew Christopher Morgan

Theses and Dissertations

Imidazoles are heterocyclic small molecules that play a major role in medicinal chemistry and drug discovery. There are several drugs in the market which contain imidazoles as the pharmacophore. Metronidazole, an imidazole containing compound, is a prominent antibiotic and antiprotozoal medication used for the treatment of a variety of infections such as amoebiasis, trichomoniasis, bacterial vaginosis, etc. The current work involves the synthesis of small molecule libraries of imidazoles derived from metronidazole using Baylis-Hillman (BH) reaction. BH reaction is a carbon-carbon bond forming reaction and involves the coupling of aldehydes or imines with activated alkenes such as acrylates, acrolein, or …

Functionalized Heterocyclics As Potential Therapeutics, Anupama Indukuri

Theses and Dissertations

Heterocyclic compounds play an important role in pharmaceutical drug development. Several natural products and biologically active compounds contain heterocyclic motifs in them. Multicomponent coupling reactions offer an excellent platform for the synthesis of diverse libraries of heterocyclic compounds. We have been working on the synthesis of novel heterocyclic small molecules utilizing reactions such as Baylis-Hillman reaction, Passerini reaction, Click reaction, reductive amination aldol condensation, etc.

In the current project, we prepared three series of heterocyclic compounds using Passerini and Baylis-Hillman reactions as key steps. Owing to the importance of heterocyclic chemistry in drug discovery and the ease of synthesis, the …

Modification And Characterization Of Chloro-Sugar Derivatives As Anti-Bacterial Agents, Mansi Jani

Theses and Dissertations

Sucralose is an artificial sugar substitute which is most commonly used sweetener among other artificial sweeteners. It is derived from sucrose through a complex chemical process that selectively substitutes three atoms of chlorine for three hydroxyl groups on sucrose molecule, which have shown some inhibition of bacterial growth in gut. The goal of the project was to substitute halide in sucralose in a way that it sustains potential anti-bacterial activity along with sweetening effect, which can be then incorporated into mouthwash formulation. Sucralose is very stable molecule and it also has other physico-chemical advantages which are suitable for our anticipated …

Synthesis Of Novel Library Of Cyanopyrrolidinyl Beta-Amino Alcohols And Matrine Alkaloids, Xiaotian Chen

Theses and Dissertations

Cyanopyrrolidines and beta-Amino alcohols are molecular scaffolds that are highly found in commercially available drugs. We developed a multi-step synthetic method to form a novel library of compounds as inhibitors that share both scaffolds toward potent and selective diabetes therapeutics. Despite the ease for the synthesis of Cyanopyrrolidines, the difficulty of forming high selective beta-Amino alcohols is challenging. We successfully find the best condition for the preference of highly selective mono-alkylation and double-alkylation products and produce them with high yield.

Matrine is an alkaloid found in plants from the genus Sophora and can produce some pharmacological effects such as anti-cancer …