Heterocyclic Compounds Commons^™

Synthesis Of 1-(4-Ethoxy-3-Methoxybenzyl)-1,10-Phenanthrolin-1-Ium Bromide And Its Evaluation As Antiplasmodium Through Heme Polymerization Inhibitory Activity (Hpia) Assay, Dhina Fitriastuti, Viny Alfiyah, Mustofa Mustofa, Jumina Jumina, Muhammad Idham Darussalam Mardjan

Makara Journal of Science

This study describes the development of N-benzyl-1,10-phenantrolinium salt as an antiplasmodium agent. The salt, that is, 1-(4-ethoxy-3-methoxybenzyl)-1,10-phenanthrolin-1-ium bromide, was prepared using vanillin as the starting material in four simple synthetic steps. First, the alkylation of vanillin using diethyl sulfate produced 4-ethoxy-3-methoxybenzaldehyde in 79% yield. Second, the reduction of the protected vanillin by NaBH₄ through the grinding method allowed us to obtain 4-ethoxy-3-methoxybenzyl alcohol in 96% yield. Next, the bromination of the benzyl alcohol under solvent-free condition led to the formation of the corresponding benzyl bromide, which in turn underwent bimolecular nucleophilic substitution with 1,10-phenanthroline to produce the desired …

Synthesis Of 5-Membered Ring Heterocycles For Alzheimer’S Disease, Daniel Fajardo

Honors Scholars & Undergraduate Research Poster Symposium Programs

The progression of Alzheimer’s disease (AD) is correlated to the degenerative activation of muscarinic acetylcholine receptors (mAChR) located in the brain. They are a family of five G-protein coupled receptors, (M1-M5), linked to functions within the central and peripheral nervous system.1 More specifically, activation of M1 with positive allosteric modulators (PAM), have shown to bind to the allosteric pocket and slow the degenerative process of AD with minimal intrinsic effects.2 Structural motifs of potent PAM activity and weak agonism proposed a synthesis of an isooxazoline compound, incorporating a 1,3-dipolar cycloaddition. The core motif of the proposed isooxazoline structure has been …

'Induction Of Apoptosis, Cytotoxicity And Radiosensitization By Novel 3,4-Dihydroquinazolinone Derivatives, Eman Ramadan, Amira Khalil

Pharmacy

Twenty new quinazolinone derivatives bearing a piperonyl moiety were designed and synthesized. The structures of the target compounds were in agreement with the microanalytical and spectral data. Compounds 4-10, 13, 14 and 17-27 were screened for their cytotoxic activity against HepG-2 and MCF-7 cancer cell lines. The target compounds showed IC₅₀ in the range of 2.46-36.85 µM and 3.87-88.93 µM for HepG-2 and MCF-7, respectively. The promising compounds 7, 19, 26 and 27 were selected to measure their EGFR inhibitory activity. The IC₅₀ values of the promising compounds were in the range of 146.9-1032.7 nM for EGFR in …

Impact Of Ketorolac On Opioid Consumption After Open Heart Surgery, Laura Neubauer, Radhan Gopalani, Kristen De Almeida, Andrea Marr-Peralto

All Publications

No abstract provided.

Gama-Lactams And The Reformatsky Reaction: New Tricks For Old Chemistry, Dylan Dupont

Honors Theses

DUPONT, DYLAN. An Alternative Synthetic Pathway to γ-Lactam Compounds

Through the Application of Novel Reformatsky-Type Chemistry. Department

of Chemistry, June 2020

ADVISOR: James C. Adrian Jr. Ph.D.

It is the intent of the present report to relate the results of our attempt to elucidate and optimize a novel preparation of γ-lactam compounds. To achieve this end, it is proposed that the use of novel Reformatsky-type chemistry may provide a viable means. Generally, it has herein been validated that employment of α-amino ketones in traditional Reformatsky chemistry will form the traditional Reformatsky ester-adduct, and that this adduct is capable of spontaneously …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks

Honors Theses

Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I concluded …

Hailey-Hailey Disease Successfully Treated With Low-Dose Naltrexone, John Moesch, Richard Miller

West Florida Division Virtual Research Day 2020

Hailey-Hailey disease (HHD) is an uncommon autosomal dominant disorder resulting from a mutation in the ATP2C1 gene resulting in dysfunction of the Golgi apparatus calcium-associated ATPase, thus interfering with intercellular calcium signaling.

HHD presents clinically as flaccid blisters and erosions in intertriginous areas, especially the axillae and groin.

The major histologic finding is acantholysis throughout the spinous layer of the epidermis, commonly referred to as a “dilapidated brick wall” appearance.

The initial lesions and associated symptoms usually develop during the second or third decade of life.

Complications of HHD include infections (bacterial, fungal, and viral), and malignant transformation (cutaneous squamous …

P-19 Anticancer Activity Of Heteroaromatic Cyanostilbenes, Joshua Rotich

Celebration of Research and Creative Scholarship

Cancer is currently the second leading killer disease. There are many different kinds of cancer that are associated with almost every organ in the human body (e.g., brain cancer, colon cancer, breast cancer, prostate cancer, blood cancer, lung cancer, etc.).

In the Biology Department, Dr. Smith and Dr. Murray are researching glioblastoma brain cancer cells. Glioblastoma is a very invasive cancer that is highly lethal. Chances of not surviving when its at stage four is more than 98%. Detecting this cancer while it is developing is difficult because symptoms are mild headache, fatigue, nausea and slight loss of weight. By …

Stable Nanopalladium Hydride In Water For Sustainable And Selective Reductions, Jesse Klus, Sachin Handa

Posters-at-the-Capitol

The synthesis of air-stable ligand-free nanopalladium hydride (PdNHx) in water was achieved and applied to various organic transformations, including (1) reduction of heteroaromatics such as (iso)quinolines, phenanthrolines, benzotriazole, and naphthyridines, (2) regio- and chemoselective reduction of nitroarenes, (3) alkyne reductions, (4) chemoselective dehalogenation, and (5) base-free detriflation. Both the synthesis of PdNHx and the reductions were carried out under mild conditions in a micellar medium using our designer surfactant PS-750-M, which eliminates the need for toxic organic solvents and extremely high hydrogen pressure and temperature. Notably, PS-750-M is also a replacement of hazardous polar-aprotic solvents. This newer approach for selective …

Heterocycle Synthesis From Quinols, Jing Wu

Dissertations, Theses, and Capstone Projects

Three cascade reactions that provide access to various heterocyclic skeletons from quinols were developed. Various substituted 1-hydroxyacridones, 4-hydroxycarbazoles and 4-hydroxy-indolin-3-ones were readily synthesized in moderate to excellent yields. The common sequential transformation involves carbamation/Michael addition/mixed Claisen condensation/decarboxylative aromatization which were realized in one-pot reactions in the synthesis of acridones and indolin-3-ones, or two-step reactions in the synthesis of carbazoles. A side reaction from oxidative dearomatization of phenols, affording iodo diaryl ethers in one step from commercial phenols, albeit in low yields, revealed an intricate mechanistic pathway. The synthesis of jaboticabin was realized in nine linear steps from commercial phloroglucinol and …

Mechanistic Studies And Derivative Effects In 1, 3, 4- Oxadiazole Synthesis Via Cyclodehydration Reactions, Evan Huggins

Undergraduate Honors Thesis Projects

In the world of pharmaceutical synthesis, research to combat foreign pathogens is always necessary. Scientists have been exploring different methods in order to synthesize the most effective compounds in antibacterial, anticancer, anti-inflammatory, and many other treatments. A key component within these versatile compounds are 1,3,4-oxadiazoles. Current methods to synthesize these compounds are inefficient. This research seeks to improve oxadiazole synthesis; however, the mechanism of this reaction is unknown. The goal of this project was to study the mechanistic pathway in the discovered, one-pot cyclodehydration synthesis of 1,3,4-oxadiazoles. In the first part of this study, a diacylhydrazine intermediate was proposed. This …

Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore, Malaika Argade

Theses and Dissertations

Alzheimer’s disease is a progressive neurodegenerative disorder generally affecting people above the age of 65 years. Even though the pathophysiological hallmarks of AD were established more than a hundred years ago, there is yet to be a drug that can stop its characteristic neuronal damage. Of the five currently FDA-approved drugs, galantamine has a unique mechanism of action. Apart from being an AChE inhibitor, galantamine can effectively potentiate (positive allosteric modulator) the effect of agonists at nAChRs at concentrations lower than those required for its action as an AChE inhibitor. Perhaps the clinical benefits observed with galantamine are associated mainly …

Synthesis Of Hydroxybenzylidene-Indolinones, Schiff Bases And N-Substituted Analogs And Their Effects On Bacterial Physiology., Catherine Eliana Cabrera, Neetu Dayal, Moloud Aflaki, Herman Sintim

The Summer Undergraduate Research Fellowship (SURF) Symposium

c-di-AMP is a global stress response regulator involved in some processes of biofilm formation and antibiotic resistance. It has become a candidate target for the development of new antibacterial treatments. Previous studies have shown that hydroxybenzylidene-indolinones can act as c-di-AMP synthase inhibitors. They also act as antibacterial and anti-biofilm inhibitors and re-sensitize resistant bacteria to methicillin and vancomycin. In this project, potent analogs of these compounds, including Schiff bases and N-substituted compounds, have been synthetized. The objective of this work is to explore the effect of these modifications on their biological activity. Base-catalyzed condensation and acid-catalyzed reactions were performed in …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker

All Master's Theses

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …

Synthesis Of Oxadeazoles With Electron Withdrawing Groups And The Analysis Of Product Yield With Bond Length, Elizabeth Ann Hall Peters

Undergraduate Honors Thesis Projects

2,5-disubstituted 1,3,4-oxadiazoles are a class of organic compound that are widely used and successful in pharmaceutical chemistry because they demonstrate strong biological activity. They are part of a larger class of compound called heterocycles, which make up most pharmaceutical drugs today. When synthesizing the compounds, higher yield means higher reactivity of the compound, and this is important for pharmaceuticals that need to have a strong biological activity. Per past studies, electron withdrawing groups on the compound allow higher, product yields. Along with electron withdrawing group addition, the bond length from electron withdrawing group and its corresponding carbon is analyzed to …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle

Articles

Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and Western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerised when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …