Physical Sciences and Mathematics Commons^™

Photo-Reactivity Of Bifunctional Naphthalene Compounds Toward Dna, Qi Zhang

Theses and Dissertations

DNA interstrand cross-link (ICL) can covalently bind two DNA strands, preventing DNA strands separation, and therefore, blocking DNA transcription and replication, which are essential biological processes for cell division. Among different methods to induce DNA interstrand cross-linking, photoinduction is an important way to activate the cross-linking reactions due to its many characteristics, such as non-invasive, controllability, selectivity and biorthogonality. My research mainly focuses on developing novel binaphthalene compounds which can be activated by 350 nm UV light to produce DNA interstrand cross-linking via alkylation. We designed and synthesized a series of binaphthalene analogues with different substituents at the position-4’ on …

Inducible Dna Interstrand Cross-Linking Agents: Design, Synthesis, Mechanism, And Biomedical Applications, Muhammad Asad Uz Zaman

Theses and Dissertations

DNA is the carrier of genetic information, making its chemical reactivity and function extremelyimportant. DNA interstrand cross-links (ICL) leads to covalent bind of two strands, which prevents the separation of double helix. DNA ICLs are the sources of the cytotoxicity of antitumor and anticancer agents. This thesis focuses on investigating the reactivity of a varieties of aromatic compounds towards DNA. Some of these molecules can be activated by photo irradiation to induce DNA ICL formation via alkylation. Others undergo activation by H2O2 to release DNA cross-linking agents. We investigated the mechanism of function of these inducible DNA cross-linking agents as …

The Activity Of Qh Ii 66 And It’S Analogs In Medulloblastoma, Melanoma And Non-Small Cell Lung Cancer Cell Lines., Taukir Ahmed

Theses and Dissertations

GABAARs (gamma-aminobutyric acid type A receptors) are transmembrane pentameric ligand-gated chloride ion channels that respond to GABA, the central nervous system's principal inhibitory neurotransmitter (CNS). The benzodiazepines (BZDs) bind between the GABAAR α+γ2-subunits at their extracellular interface. The binding of ligands to distinct subunits of GABAA receptors, notably the α1-6β2/3γ2 ion channels, can have a wide range of effects on brain activities. The sedative, ataxic, amnesic, anticonvulsant, and addictive actions of GABAARs' α1-subtype selective ion channels should be avoided, except for the anticonvulsant and anxiolytic effects, while creating ligands for this BZ allosteric modulatory site. Many studies have linked the …

Design And Synthesis Of Chiral And Achiral Benzodiazepines And Imidazodiazepines As Α–Subtype Selective Gabaar Positive Modulators To Treat Schistosomiasis, Epilepsy, Asthma And Some Mental Disorders, Md Yeunus Mian

Theses and Dissertations

Part I: Design, synthesis, and biological evaluation of non-sedating anti-schistosomal agents

Schistosomiasis is a parasitic flatworm infection with only one drug therapy currently on the market, praziquantel. An old lead identified by Roche, meclonazepam (US Patent 4031078A) displayed antiparasitic efficacy but was not pursued due to dose-limiting sedation in human clinical trials (S. Afr. Med J. 1979 Apr 14;55(16):617-8, PMID: 380021). However, given the superior spectrum of activity meclonazepam displays relative to praziquantel (which is unable to cure immature parasites within the host) and advances in the understanding of benzodiazepine SAR at human GABAARs, the study of this benzodiazepine was …

Part I: Synthesis Of Quinolones For Inhibition Of The Β-Barrel Assembly Machine In Gram Negative Bacteria; Part Ii: Synthesis Of Azo Dye Sensors For Detection Of Metal Ions In Aqueous Environments, Katryna Williams

Theses and Dissertations

Part I: Antibiotic resistance in Gram-negative bacteria is a growing cause of concern worldwide. Thousands of people die from antibiotic resistant bacteria every year. The β-Barrel Assembly Machine (BAM) in Gram-negative bacteria plays a role in antibiotic resistance as its porin, BamA, can regulate which molecules enter the cell, meaning it can prevent antibiotics from entering the bacterial cell. BamA exists in an open and closed form and is only selective in its closed form. BamA opens and closes through the H-bonding of two intramolecular β-strands. It is theorized that the creation of a β-sheet mimetic, based on work done …

Guest Host Chemistry Part I: The Synthesis Of Metal Selective Sensors Part Ii: The Synthesis Of Antibiotic Precursors And Intermediates, Trevor Moss Hagemann

Theses and Dissertations

Part 1: Metal Selective Sensors

The work herein describes the creation of a library of sensors for the detection of metal ions in aqueous systems. The solid support these dyes are attached to facilitates a continuous measurement of metal ion concentrations in aqueous systems. The sensors are based on an azo dye core structure wherein detection of metal ions is observed by the change in absorbance of the dye upon binding. These sensors are capable of detecting metal ions in the ppb range, specific dyes interacting with specific metal ions cause distinct spectral changes, providing substantial information. the aggregate response …