The chemistry of quinonline-5,8-dione as a functional group is a developing field because of its various biological aspects. Lavendamycin and streptonigrin are known antibiotic, antitumor agents containing the quinolone-5,8-dione functional group believed to provide their antitumor properties. Most cancer cells show an elevated level of NQO1 enzyme which activates lavendamycin to act as an antitumor agent. The research goal is to explore different synthetic methods and reactions to produce novel quinolone-5,8-dione analogues with unique structural features while keeping the selective cytotoxicity. Lavendamycin contains a β-carboline and streptonigrin has a substituted pyridine connected to the 2-position of the quinolone-5,8-dione. The overall goal of this project will develop synthetic methods to create 1,2,3-triazoles and 1,2-diazoles attached to the quinoline moiety from azides and diazonium salts, respectively. In order to accomplish this, 8-hydroxyquinoline undergoes through a four step synthesis to install an azide at the two position of the quinoline ring. 8-Hydroxyquinoline was oxidized to produce 8-hydroxyquinoline-N-oxide, converted into 8-acetoxy-2-hydroxyquinoline with acetic anhydride, reacted with POCl3 to produce 2-chloro-8-hydroxyquinoline, and treated with sodium azide to form 2-azido-8-hydroxyquinoline. However it was found that the product cyclized to yield 8-hydroxy-tetrazole[1,5-a]quinoline. In the quinoline-5,8-dione synthesis, 7-amidoquinoline-5,8-dione is prepared through a three step synthesis. 8-Hydroxquinoline was nitrated to form 8-hydroxy-5,7-dinitroquinoline, hydrogenated/acylated to give 5,7-diacetamido-8-acetoxyquinoline, and oxidized to yield 7-acetamidoquinoline-5,8-dione. In order to reach the end of this project, the four step tetrazole and the three step quinoline-5,8-dione syntheses required merging. Further research will focus on the optimization of these syntheses. / Synthesis of 8-hydroxy-tetrazole [1,5-a] quinoline -- Synthesis of 7-amino-quinoline-5,8-dione -- Novel synthesis of quinoline-5,8-dione analogues. / Department of Chemistry

No description available.

The chapter of stereochemistry which deals with the attempted resolution of saturated tervalent nitrogen compounds is a long and interesting one, but is as yet incomplete. The problem has been attacked in many ways; but despite the great amount of work which has been carried out the failure to achieve the resolution of such compounds has been complete.

No description available.

Doctor of Philosophy / Department of Chemistry / Duy H. Hua / The first section of this thesis deals with the synthesis of substituted quinolines and its bioactivities against gap junction. Cancer cells are characterized by down regulated or altered gap junction intercellular communication (GJIC) activities; enhancement of GJIC would provide a pathway for the delivery of anticancer drugs. Our computational studies using Autodock found binding interactions between gap junction channels and substituted quionlines (code name PQs). Thus, a serial of PQ compounds were synthesized and their activities against GJIC were tested. Among these synthesized PQs, 6-Methoxy-8-[(3-aminopropyl) amino]-4- methyl-5-(3-trifluoromethyl- phenyloxy)quinoline (PQ1) can specifically enhance GJIC activity of T47D cells without affecting the normal MECs. The PQ1 induced apoptosis can spread throughout the gap juctions, consequently cause the decrease of cell viability and colony growth. PQ1 can attenuate tumor growth of xenograft tumors in Nu/Nu mice. Compound 7 (code PQ11) which has an IC50 of 15.6nM against T47D cancer cell, is a promising candidate for further pharmacological studies. The second section of this thesis deals with the synthesis and anticancer bioactivities of PEG-PEI based nanogels. Nanogels were synthesized, encapsulated with anticancer drugs, and loaded to stem cells. Stem cells can target at the cancer cell and release the nanogel and anticancer drug to kill the cancer cell. The nontoxic PEG-PEI nanogel which can be loaded to stem cells was successfully synthesized by doubly treatment of PEI with activated PEG. Based on this nontoxic nanogel, two other types of nanogels were synthesized. In one type of nanogel, an anticancer drug, SN38 was modified and attached to the nontoxic nanogel via a tetra-peptide linker. This tetra peptide can be recognized and cut by legumain, a protein that highly over expressed in many tumors, to release the drug to tumors. In the other type of nanogel, straptavidin was attached to the nanogel which can bind to biotin and recognized by tumor. The result indicated this type of nanogel can be loaded to stem cells within 15 minutes.

Submitted in fulfilment of the requirements of the Degree of Master of Technology: Chemistry, Durban University of Technology. 2014. / In this study, we report the synthesis of three quinolone bearing imidazole derivatives 2, 3 and 4 and two quinolone bearing BODIPY dyes 5 and 7. In the synthesis of 2, 3 and 4, the first step was the preparation of the starting compound 2-chloro-3-formyl quinoline (1); the Vilsmeier-Haack cyclisation protocol was used. Compound 1 was used with the appropriate diamine, together with POCl3 to produce 2, 3 and 4. These compounds were characterized by IR, 1H-NMR and 13C-NMR. In the synthesis of 5, compound 1 was used whilst 6 was used for the synthesis of 7. This was via. a one-pot synthesis using conventional reflux apparatus and Schlenk technique. These compounds were characterized by IR, 1H-NMR and 13C-NMR. Four other BODIPY dyes were also synthesized but their purification by column chromatography were unsuccessful. However a HPLC method was developed using 2 as a model; the best eluting solvent was 65 % methanol. After synthesis, 2, 3, 4, 5 and 7 were used for spectroscopic studies by UV-visible and fluorescence spectroscopy. In the UV-visible studies, 2, 3 and 4 were dissolved, separately, in five solvent viz. ethanol, methanol, dichloromethane, chloroform and acetonitrile. The UV profile of each compound was obtained and the maximum absorbance was then used for fluorescence studies. In the fluorescence studies, all the compounds displayed a fluorescence nature when excited with the various wavelengths. The fluorescence properties, namely Stoke shift, quantum yield, life time, molar absorptivity and brightness, were investigated to establish the properties of each compound in all five solvent systems. The Stoke shift was evident in all compounds and the quantum yields were below one which indicates no other electron transfer mechanisms occurring. The results displayed a favorable response and this further lead to analysis of the synthesized compounds for it potential application as a chemosensor. Eight metal ions were used to investigate this property. All eight metal ions, when reacted with the synthesized compounds, as ligands, showed chemosensor properties, viz. photon induced electron transfer, inter-molecular charge transfer and fluorescence resonance electron transfer, as a quenching and enhancement of emission and excitation peaks were observed. The compounds were further investigated for its potential for its use as a photovoltaic cells. The energies of the compounds were obtained from the analyses of the reflectance and transmission spectra. It was found that the synthesized compounds displayed properties which were positive for its use as a photovoltaic cell. Biological analyses using molecular docking analyses and MTT assays were conducted to determine the use of these as an anti-cancer drug. Compounds 2 and 3 formed hydrogen bonds with GLU 25 and LEU 27, respectively with MDM2-p53 proteins. Following the molecular docking studies, the MTT assay was performed on all five synthesized compounds. The BODIPYs with the quinoline moieties demonstrated a reduction in the rate of A549 cell proliferation when compared to the imidazole and benzimidazoles; this was observed for compounds 5 and 7. Further, a comparison between imidazoles clearly shows that compounds 3 and 4 also decreased cell proliferation. In contrast compound 2 exhibited an increased rate of cell proliferation. The optical density of the control cell, is much higher that the plates for concentration 31.25 µg/ mL to 500 µg/ mL. However 2 cannot be discarded; this compound clearly shows that it possesses anti-hyperglycaemic properties and further studies are recommended.

No description available.

by Lawrence Tin-chi Law. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 96). / acknowledgements --- p.iii / ABSTRACT --- p.iv / CONTENTS --- p.v / ABBREVIATION --- p.vii / Chapter CHAPTER I --- METALLATION OF 8-METHYLQUINOLINE / Chapter 1.1 --- INTRODUCTION --- p.1 / Chapter 1.1.1 --- A Brief Review of Metal-Alkyl Chemistry --- p.1 / Chapter 1.1.2 --- General Considerations --- p.2 / Chapter 1.1.3 --- 8-Methylquinoline as Ligand Precursor --- p.8 / Chapter 1.1.4 --- Metallations by Organolithium Compounds --- p.9 / Chapter 1.1.5 --- Other Methods for Metallations --- p.16 / Chapter 1.1.6 --- Aim of the Present Work --- p.21 / Chapter 1.2 --- RESULTS AND DISCUSSION --- p.24 / Chapter 1.2.1 --- Reactions of 8-Methylquinoline with Organolithium Reagents --- p.26 / Chapter 1.2.2 --- Synthesis of Grignard Reagent --- p.35 / Chapter 1.2.3 --- Attempted Metal-Halogen Exchange Reaction at Low Temperature --- p.39 / Chapter 1.2.4 --- Metallation of 8-methylquinoline by Lithium Diisopropylamide --- p.40 / Chapter 1.3 --- EXPERIMENTAL FOR CHAPTER I --- p.43 / Chapter 1.4 --- REFERENCES FOR CHAPTER I --- p.53 / Chapter CHAPTER II --- SYNTHESIS AND CHARACTERISATION AND STRUCTURE OF SOME MAIN GROUP 14 ALKYLS / Chapter 2.1 --- INTRODUCTION --- p.58 / Chapter 2.1.1 --- General Aspects of Group 14 Organometallic Compounds --- p.58 / Chapter 2.1.2 --- Group 14 Organometallic Confounds --- p.59 / Chapter 2.1.3 --- Subvalent Group 14 Metal Alkyls --- p.63 / Chapter 2.2 --- RESULTS AND DISCUSSION --- p.67 / Chapter 2.2.1 --- Synthesis of Five Co-ordinated Tin (IV) Compound --- p.67 / Chapter 2.2.2 --- Molecular Structure of [Sn{8-(CHSiMe3)C9H6N}Ph2Cl] --- p.70 / Chapter 2.2.3 --- Synthesis of Group 14 Subvalent Metal Complexes --- p.74 / Chapter 2.3 --- EXPERIMENTAL FOR CHAPTER II --- p.76 / Chapter 2.4 --- REFERENCES FOR CHAPTER II --- p.79 / Chapter CHAPTER III --- SYNTHESIS AND CHARACTERISATION OF SOME GROUP 12 (ZINC AND CADMIUM) METAL DIALKYLS / Chapter 3.1 --- INTRODUCTION --- p.81 / Chapter 3.1.1 --- A General Aspect of Group 12 Organometallics --- p.81 / Chapter 3.2 --- RESULTS AND DISCUSSION --- p.88 / Chapter 3.2.1 --- Synthesis of Group 12 Organometallic Confounds --- p.88 / Chapter 3.2.2 --- Molecular Structure of [Cd{8-(CHSiMe3)C9H6N}(tmeda)Cl] --- p.91 / Chapter 3.3 --- EXPERIMENTAL FOR CHAPTER III --- p.93 / Chapter 3.4 --- REFERENCES FOR CHAPTER III / APPENDIX I / Chapter 1. --- GENERAL PROCEDURES --- p.97 / Chapter 2. --- PHYSICAL AND ANALYTICAL MEASUREMENTS --- p.100 / APPENDIX II / LIST OF SELECTED 1H NMR SPECTRA --- p.101

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Bibliography: leaves 285-288. / by Joseph Francis Cocchetto. / Ph.D.

There are currently no ideal treatments or acceptable vaccines for cutaneous leishmaniasis, a worldwide health problem caused by infection with a number of species of the dimorphic protozoa Leishmania. Therefore, there is an urgent need to search for simple, safe, effective, and affordable treatments. Imiquimod is an immune-response modifying agent. Recently, 5% imiquimod cream (Aldara(TM)) received approval by the Food and Drug Administration in the United States and is currently available for the treatment of external genital and perianal warts caused by human papillomavirus infection. The antiviral activity of this drug is mediated through stimulation of cytokine release from many cell types including macrophages resulting in a local immune response at the site of application. Moreover, imiquimod has been shown to enhance cell-mediated immune responses (CMIR). Since imiquimod activates macrophages, the exclusive host cells of Leishmania, and stimulates CMIR which are required for host defence against Leishmania, we have investigated the potential of using imiquimod and its related compound, S-28463, as agents for treating leishmaniasis. It is demonstrated within that imiquimod and S-28463 effectively stimulated leishmanicidal activity both in vitro in macrophages and in vivo in a mouse model. These compounds also stimulated signal transduction associated with the induction of nitric oxide synthesis in macrophages. Imiquimod and S-28463 induced leishmanicidal activity in macrophages in the absence of any other cell types. We have demonstrated that S-28463 generated macrophage leishmanicidal activity by inducing genes involved in macrophage activation and inflammatory responses. Finally, we have also performed an analysis on the influence of L. donovani on macrophage gene expression using a cDNA array analysis, a similar methodology to study the effect of S-28463 on macrophage gene expression. Intramacrophage infection with L. donovani was shown to cause general