Heterocyclic Compounds Commons^™

Synthesis Of Selenotryptophan For Protein Elucidation, James P. Reiselman

Belmont University Research Symposium (BURS)

Through complex intermolecular and intramolecular forces, proteins conformationally change to form complex 3-d geometry that carries out biochemical processes and mapping their structures is becoming a field of interest in the biological community. Techniques for modeling protein’s structure typically follow the path of X-ray crystallography, which has an intrinsic phase problem that can make reading the electron density map they produce very difficult. This can be mitigated by appending a heavy-atom containing amino acid analogue into a crystal sample of the protein being studied. A selenium containing tryptophan analogue will be synthesized to be appended into proteins as a ...

Design And Synthesis Of Small Molecular Probes For Cns And Kidney Disorders, Swagat H. Sharma

Theses & Dissertations

The G protein regulated inwardly rectifying potassium channels (GIRK) are a family of inwardly rectifying potassium channels and are key effectors in signaling pathways. GIRK 1/2 channel subunit, predominantly found in the brain, is involved pathophysiology of various neurological disorders including, but not limited to, epilepsy, anxiety, Parkinson's, pain, reward, and addiction. Previously, our laboratory had identified a series of urea containing molecules as GIRK1/2 preferring activators. Unfortunately, the urea series suffers from significant PK liabilities (solubility, brain penetration and high clearance). The chapter 1 of the dissertation describes our efforts in developing three new series of ...

Dz-Bau2021-14n As Novel Pyrazolopyridine Nanocrystals: Appraisal Of Anticancer Activity Against Hct-116 And Ht-29 Colorectal Cancer Cell Lines, Zahra Kassem, Soumaiah Abou Staiteieh, Jamal Nasr, Amina Mneimneh, Ali Youssef, Nadine Darwiche, Doaa Issa, Raghida Bou Merhi, Mohammed Mehanna

BAU Journal - Health and Wellbeing

Mentioning DZ-BAU2021-14 (C₁₉H₁₇N₅O₂,347.370 g/mol) developed in BAU Labs, its promising preliminary antitumor effect nominated it to be selected as a lead antiproliferative compound against colorectal cancer cell lines owing to its proved Cyclin Dependent Kinase 2 (CDK2) inhibition (Kassem et al., 2021). Solving many problems restricting traditional cancer therapy, nanotechnology is offering safety margins and targeted delivery of poorly soluble drug. The potential effect of this compound was combined with the advantages of nanotechnology, precisely nanocrystals to achieve better antiproliferative and hopeful less cytotoxic patterns. The nanocrystals DZ-BAU2021-14N were prepared ...

Preparation Of Meta-Nitrobenzoylhydrazone Ferrocenoylacetone And Synthesis On Its Basis, Zilola Abduraxmonovna Sulaymonova, Bako Bafayevich Umarov Doctor Chemical Science, Professor

Chemical Technology, Control and Management

β-diketone-ferrocenoylacetone was obtained by Claisen condensation. Meta-nitrobenzoylhydrazone of ferrocenoylacetone (H₂L) was synthesized by the interaction of meta-nitrobenzoic acid hydrazide with ferrocenoylacetone. On its basis, complexes with copper(II) and nickel(II) ions were synthesized. The obtained compounds were characterized by the methods of elemental analysis, IR-, ¹H NMR andelectronic spectroscopy. The research results showed that H₂L in solution exists in the form of a tautomeric mixture: hydrazone, α-hydroxyazine, and cyclic 5-hydroxypyrazoline forms. According to the results of IR and ¹H NMR spectra, the complexes were assigned a planar-square structure, and in them the doubly ...

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 ...

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 ...

Heterocyclic Amines And Arylamine N-Acetyltransferase 2 Polymorphism In Pathogenesis Of Insulin Resistance., Kennedy M. Walls

Electronic Theses and Dissertations

Heterocyclic amines (HCAs) are formed when cooking meats at high temperatures or for long periods of time, and their major metabolic pathway includes hepatic N‑hydroxylation by CYP1A2 followed by O-acetylation by N-acetyltransferase 2 (NAT2). NAT2 is a highly polymorphic gene involved in metabolism of drugs and xenobiotics, and its single nucleotide polymorphisms (SNPs) produce phenotypes characterized as slow, intermediate, or rapid acetylator. Recent studies have documented associations between HCAs and insulin resistance and between certain NAT2 phenotypes and insulin resistance. In this study, we demonstrated that NAT2 activity and exposure to certain HCAs may alter cellular glucose ...

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 ...

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 ...

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 ...

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 ...

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 ...

Regional Vitiligo Induced By Imiquimod Treatment For In-Transit Melanoma Metastases, Elizabeth Tkachenko, Jennifer Y. Lin, Rebecca I. Hartman

Open Access Publications by UMass Chan Authors

Imiquimod is a topical immunomodulator used for the treatment of viral warts and superficial basal cell carcinoma and as an emerging therapy for lentigo maligna and cutaneous melanoma metastases. Vitiligo-like depigmentation has been described as a local adverse effect of topical imiquimod therapy for melanoma1 and at distant sites in patients treated with combination topical monobenzone-imiquimod for metastatic melanoma.2 We present a case in which topical imiquimod resulted in both the resolution of in-transit metastatic melanoma and the depigmentation of local and regional skin, suggesting a regional lymphatic effect of this localized topical treatment.

Synthetic Approaches Towards Novel Isoform Selective Pi3k Inhibitors And Their Biological Activities Against Prostate Cancer Cells, Idris Wazeerud-Din

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The development of novel imidazopyridines, which includes both tetrahydroimidazo[1,5-a]pyridine (rIMP) and imidazo[1,5-a]pyridine (IMP) was investigated using conventional and microwave induced procedures that afforded compounds at high yield of 88-96%. rIMP was synthesized using a two-step procedure that involved the microwave synthesis of IMP, then the reduction of the pyridine moiety of the fused imidazopyridine rings using 10% Pd/C and hydrazine monohydrate. The microwave synthesis of imidazopyridines involved the one pot reaction of 2-benzoylpyridine, substituted benzaldehyde and ammonium formate in acetic acid under open vessel microwave conditions, which resulted in products within 40 minutes ...

Deconvolution Of Subcellular Protrusion Heterogeneity And The Underlying Actin Regulator Dynamics From Live Cell Imaging [Preprint], Chuangqi Wang, Hee June Choi, Sung-Jin Kim, Aesha Desai, Namgyu Lee, Dohoon Kim, Yongho Bae, Kwonmoo Lee

UMass Chan Medical School Faculty Publications

Cell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanistic understanding of protrusion activities is usually based on the ensemble average of actin regulator dynamics at the cellular or population levels. Here, we establish a machine learning-based computational framework called HACKS (deconvolution of Heterogeneous Activity Coordination in cytosKeleton at a Subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion in migrating cells. HACKS quantitatively identifies distinct subcellular protrusion phenotypes from highly heterogeneous protrusion activities and reveals their underlying actin regulator dynamics at the leading edge. Furthermore, it can identify specific subcellular protrusion phenotypes susceptible to pharmacological perturbation ...

C. Elegans Multidrug Resistance Protein 5 (Mrp-5) Transports Vitamin B12 From The Intestine To The Gonad To Support Embryonic Development [Preprint], Huimin Na, Olga Ponomarova, Gabrielle E. Giese, Albertha J. M. Walhout

UMass Chan Medical School Faculty Publications

Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and for methylmalonyl-CoA mutase to catabolize the short chain fatty acid propionate. In the nematode Caenorhabditis elegans, maternally supplied vitamin B12 is required for the development of her offspring. However, the mechanism for exporting vitamin B12 from the mother to her offspring is not yet known. Here, we use RNAi of more than 200 transporters with a vitamin B12-sensor transgene to identify the ABC transporter MRP-5 as a candidate vitamin B12 exporter. We show that injection of vitamin B12 into the gonad of ...

Sodium Channel Nav1.3 Is Important For Enterochromaffin Cell Excitability And Serotonin Release, Peter R. Strege, Kaitlyn Knutson, Samuel J. Eggers, Joyce H. Li, Fan Wang, David Linden, Joseph H. Szurszewski, Lorin Milescu, Andrew B. Leiter, Gianrico Farrugia, Arthur Beyder

Open Access Publications by UMass Chan Authors

In the gastrointestinal (GI) epithelium, enterochromaffin (EC) cells are enteroendocrine cells responsible for producing > 90% of the body's serotonin (5-hydroxytryptamine, 5-HT). However, the molecular mechanisms of EC cell function are poorly understood. Here, we found that EC cells in mouse primary cultures fired spontaneous bursts of action potentials. We examined the repertoire of voltage-gated sodium channels (NaV) in fluorescence-sorted mouse EC cells and found that Scn3a was highly expressed. Scn3a-encoded NaV1.3 was specifically and densely expressed at the basal side of both human and mouse EC cells. Using electrophysiology, we found that EC cells expressed robust NaV1.3 ...

The Dopamine Transporter Recycles Via A Retromer-Dependent Postendocytic Mechanism: Tracking Studies Using A Novel Fluorophore-Coupling Approach, Sijia Wu, Rita R. Fagan, Chayasith Uttamapinant, Lawrence M. Lifshitz, Kevin E. Fogarty, Alice Y. Ting, Haley Melikian

UMass Chan Medical School Faculty Publications

Presynaptic reuptake, mediated by the dopamine (DA) transporter (DAT), terminates DAergic neurotransmission and constrains extracellular DA levels. Addictive and therapeutic psychostimulants inhibit DA reuptake and multiple DAT coding variants have been reported in patients with neuropsychiatric disorders. These findings underscore that DAT is critical for DA neurotransmission and homeostasis. DAT surface availability is regulated acutely by endocytic trafficking, and considerable effort has been directed toward understanding mechanisms that govern DAT's plasma membrane expression and postendocytic fate. Multiple studies have demonstrated DAT endocytic recycling and enhanced surface delivery in response to various stimuli. Paradoxically, imaging studies have not detected DAT ...