Thesis (Honors)--Liberty University Honors Program, 2008. / Includes bibliographical references.

Thesis (Ph.D)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Pharmacology and Toxicology. Title from title-page of electronic thesis. Bibliography: leaves 134-160.

published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

No description available.

In vitro selection for multidrug resistance (MDR) and retroactive clinical studies have established an important role for both P-glycoprotein (P-gp) and the Multidrug Resistance-associated Protein (MRP) in conferring pleiotropic resistance to several structurally dissimilar hydrophobic drugs. Both P-gp and MRP are ABC transporters which when overexpressed in tumour cells are capable of enhancing drug efflux, resulting in a drug accumulation deficit. Paradoxically, acquisition of the MDR phenotype frequently results in newfound hypersensitivity to a different group of drugs. This thesis investigates the collateral sensitivity of the P-gp-bearing CHO cell line CH$ sp{ rm R}$ C5 to the calcium channel blocker, verapamil (VRP). In addition, the hypersensitivity of the MRP-bearing SCLC line H69AR to BSO, a depleter of glutathione (GSH), is herein examined. Although VRP clearly induced heightened levels of p53-independent apoptosis in CH$ sp{ rm R}$ C5 cells, blockage of calcium channels was not involved in the cytotoxicity of the drug. BSO clearly killed through depletion of GSH, apparently resulting in heightened levels of necrosis in H69AR cells. In both cases, decreased expression of the Bcl-2 gene appeared to result in hypersensitivity of MDR cells to the toxic effects of BSO and VRP.

No description available.

The primary aim of this thesis was to synthesize a new class of peptide mimics derived from N-acylisatins and to investigate various methodologies for their synthesis. N-Acetylisatin 15 and its derivatives 39 and 40 were found to undergo facile nucleophilic ring-opening with amino acid esters yielding a range of 2-acetamidophenylglyoxylamide derivatives in moderate to good yields. This type of reaction was also found to work for di- and tripeptide methyl ester hydrochlorides leading to a range of N-glyoxylamide peptide mimics. The methodology of the reaction conditions was further extended to N,N′-oxalyl bisisatins 17 and 134, and 1,3,5-tris(2,3-dioxoindoline-1-carbonyl)benzene 168 substrates and their reaction with amino acid esters gave a new range of C,C′-linked-bis-glyoxylamide peptide mimics and C,C′,C′′-linked tris-glyoxylamide peptide mimics respectively. Meanwhile, reactions of N-acylisatins with 1,10-diaminodecane 155 and tris(2-aminoethyl)amine 167 gave the corresponding bis and tris-glyoxylamides. In the event of introducing amino acids at the N-1 position of isatin 9, a range of NH protecting groups for the synthesis of N-protected amino acid acyl isatins 193 were examined. It was found that the phthalamido group, e.g. phthaloylglycine 197, was the best protecting group for the introduction of a glycine unit at the N-1 position of isatin 9. Additionally, a viable and interesting alternative approach utilizing N-succinyl acylisatin 158 as the starting material was also demonstrated. In continuation of our interest in the peptidomimetic approach, a new class of cyclic peptide mimics using Grubbs?? ring-closing metathesis approach was also successfully synthesized. A range of bis-O-allyl substrates 237, 240, 242 and 246 were prepared from reaction of the corresponding N-acylisatins with L-valine allyl ester hydrochloride 236 and 1,10- diaminodecane 155 respectively. High conversion yields of the target macrocyclic systems 238, 241 and 243 were observed when the bis-Oallyl substrates were irradiated with Hoveyda-Grubb catalyst in a microwave reactor. These latter studies will provide a synthetically versatile platform for the future design of potential new drugs candidates against Gram-positive bacterial infections

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Thesis (Ph.D.). / Written for the Dept. of Chemistry. Title from title page of PDF (viewed 2007/08/29). Includes bibliographical references.

Thesis (M Nursing)--Montana State University--Bozeman, 2009. / Typescript. Chairperson, Graduate Committee: Christina Sieloff. Includes bibliographical references (leaves 55-59).