Graduation date: 1991

No description available.

Capillary Electrophoresis (CE) is a high resolution analytical technique that may be employed in the separation and quantification of a wide range of analytes. The enormous efficiency obtained in CE are well suited for complex mixtures in which resolution of a large number of peaks in a short time is desirable. Therefore, CE has a promising future in pharmaC-eutical analysis. The separation mechanism of CE is based on the differential electrophoretic mobility of the solutes inside a buffer filled capillary upon the application of a voltage. Capillary electrophoresis is especially suitable for ionic species. The full potential of this technique can only be realised through the manipulation of numerous experimental parameters. In the present study, a CE method has been developed for the analysis of the macrolide antibiotics: erythromycin, oleandomycin, troleandomycin and josamycin. The selection of initial analysis conditions and optimisation of selectivity are reviewed. A systematic approach to method development was used to maximise analyte differential electrophoretic mobilities, by adjusting the pH. Thereafter, the influences of electrolyte molarity and electrolyte additives were investigated. In addition, some instrumental parameters, such as capillary length emf diameter, applied voltage and injection conditions were varied. The effect of the sample solvent and oncapillary concentration techniques such as FASI, were investigated. Also, the influence of injecting a water plug on the quantity of sample injected was demonstrated. Full resolution was achieved with the addition of methanol to the electrolyte. The applicability of CE for the assay of erythromycin and its related substances was investigated. Two methods were developed and successfully validated using CE: one for the quantitative determination of erythromycin alone and another for erythromycin related substances in the presence of large quantities of erythromycin A. Several related substances and impurities that result from the fermentation process used to produce erythromycin as well as degradation products are known to be present in commercial sa~ples. These impurities include erythromycin B, C, D, E, F, erythromycin enol ether, anhydroerythromycin and N-demethylerythromycin. Currently both the USP and BP official assays for the analysis of erythromycin involve the use of microbiological assays. These methods are limited as they are unable to differentiate between erythromycin and its related substances and degradation products. Furthermore, the microbiological assays are time-consuming and tedious to perform. 11 The CE methods developed for the analysis of erythromycin and for its related substances were fully validated in terms of precision, linearity, accuracy, sensitivity and stability. In addition, erythromycin was subjected to six stress modes and the stressed samples were analysed. An intemal standard was employed to provide acceptable precision for the migration time « 1.80 % RSD) and peak area « 4.44 % RSD). Optimum sensitivity was obtained using low UV wavelengths, with LOO values of less than 10 % for the related substances. The developed method was accurate for erythromycin C, anhydroerythromycin and N-demethylerythromycin, even in the presence of large concentrations of the parent. The method for~ erythromycin related substances was applied to the determination of impurities in three commercial erythromycin bases. The CE methods developed were rapid, precise, specific and stability-indicating and may be used to provide additional information to augment that attained by HPLC for purity assessment and in stability studies of erythromycin. Capillary electrophoresis is a simple, cost-effective technique that is capable of generating high quality data. This technique will become firmly established within pharmaceutical analysis for main peak and related impurity determination assays as familiarity becomes more widespread across the pharmaceutical industry and improvements in instrumentation are performed.

No description available.

No description available.

No description available.

With antimicrobial resistance to current drugs steadily rising, the development of new antibiotics with novel mechanisms of action has become an imperative. The majority of life-threatening infections worldwide are caused by "ESKAPE" pathogens which are encountered in more than 40% of hospital-acquired infections, and are resistant to the majority of commonly used antibiotics. Naturally occurring cyclic depsipeptides, microbial secondary metabolites that contain one or more ester bonds in addition to amide bonds, have emerged as an important source of pharmacologically active compounds or lead structures for the development of novel antibiotics. Some of those peptides are either already marketed (daptomycin) or in advanced stages of clinical development (ramoplanin). Structurally simple, yet potent, fusaricidin/LI-F and lysobactin families of naturally occurring antibiotics represent particularly attractive candidates for the development of new antibacterial agents capable of overco ming infections caused by multidrug-resistant bacteria. These natural products exhibit potent antimicrobial activity against a variety of clinically relevant fungi and Gram-positive bacteria. Therefore, access to these classes of natural products and their synthetic analogs, combined with elucidation of their mode of action represent important initial steps toward full exploitation of their antmicrobial potential. This dissertation describes a general approach toward the solid-phase synthesis of fusaricidin/LI-F and lysobactin analogs and an extensive structure-activity relationship (SAR) study. We have devised a simple and robust preparation strategy based on standard Fmoc solid-phase peptide synthesis protocols. / The SAR study revealed key structural requirements for fusaricidin/LI-F and related cyclic lipopeptides antibacterial activity, including the presence of the guanidino moietly at the end of the lipidic tail, hydrophobic amino acid residues, and peptide conformation Moreover, substitution of the ester bond with an amide bond significantly improved stability under physiologically relevant conditions and reduced toxicity. In addition, we have shown that these antibacterial peptides exert their mode of action via a novel mechanism, which invloves bacterial membrane interactions, followed by peptide internalization. Altogether, the research described in this dissertation demonstrates that new antibiotics derived from fusaricidin/LI-F natural products, have the potential to meet the challenge of antibiotic resistance in Gram-positive bacteria. / by Nina Bionda. / Thesis (Ph.D.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Thesis (MTech Biomedical Technology)) ---Cape Peninsula University of Technology, 2008 / Resistance to antibiotics has been acknowledged as a major global public health problem. The use of peptides to provide alternatives to combat multi drug resistant organisms is of current relevance to overcome antibiotic resistance. The high deversity of amphibian skin peptides render these animals a potential source for the discovery of novel drugs.

Ko Mui Lam. / Thesis submitted in: December 2003. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 84-100). / Abstracts in English and Chinese. / Chapter Chapter 1 --- Introduction --- p.1 / Chapter A. --- Antibiotic use and resistance --- p.1 / Chapter B. --- Selection of resistant strains by antibiotics --- p.2 / Chapter C. --- Fluoroquinolones --- p.5 / Chapter D. --- β-Lactams --- p.8 / Chapter E. --- Aminoglycosides --- p.9 / Chapter F. --- Salmonella sp --- p.9 / Chapter a. --- Microbiology and clinical significance --- p.9 / Chapter b. --- Antimicrobial susceptibilities --- p.10 / Chapter G. --- Escherichia coli --- p.14 / Chapter a. --- Microbiology and clinical significance --- p.14 / Chapter b. --- Antimicrobial susceptibilities --- p.15 / Chapter H. --- Pseudomonas aeruginosa --- p.18 / Chapter a. --- Microbiology and clinical significance --- p.18 / Chapter b. --- Antimicrobial susceptibilities --- p.18 / Chapter I. --- Objectives --- p.22 / Chapter Chapter 2 --- Materials and Methods --- p.23 / Chapter A. --- Bacterial strains --- p.23 / Chapter B. --- Methods --- p.23 / Chapter a. --- Identification --- p.23 / Chapter i) --- Salmonella --- p.23 / Chapter ii) --- Escherichia coli --- p.24 / Chapter iii) --- Pseudomonas aeruginosa --- p.24 / Chapter b. --- Antimicrobial susceptibility testing --- p.24 / Chapter i) --- Determination of minimal inhibitory concentrations (MICs) of antibiotics --- p.24 / Chapter ii) --- "Determination of the antimicrobial susceptibility of Salmonella sp, Escherichia coli and Pseudomonas aeruginosa by the breakpoint method" --- p.28 / Chapter c. --- Effects of antimicrobial agents on the development of resistant mutants --- p.28 / Chapter Chapter 3 --- Results --- p.32 / Chapter A. --- Antimicrobial susceptibilities --- p.32 / Chapter B. --- Effects of fluoroquinolones on the development of resistance --- p.36 / Chapter a. --- Salmonella sp --- p.38 / Chapter b. --- Escherichia coli --- p.40 / Chapter c. --- Pseudomonas aeruginosa --- p.46 / Chapter C. --- Effects of β-lactams on the development of resistance --- p.49 / Chapter a. --- Salmonella sp --- p.49 / Chapter b. --- Escherichia coli --- p.53 / Chapter c. --- Pseudomonas aeruginosa --- p.56 / Chapter D. --- Effects of aminoglycosides on the development of resistance --- p.60 / Chapter a. --- Salmonella sp --- p.60 / Chapter b. --- Escherichia coli --- p.68 / Chapter c. --- Pseudomonas aeruginosa --- p.68 / Chapter Chapter 4 --- Discussion --- p.76 / References --- p.84 / List of Tables / Chapter I-1 --- Antimicrobial susceptibilities of salmonellae reported in the literature --- p.12 / Chapter I-2 --- Antimicrobial susceptibilities of Escherichia coli reported in the literature --- p.16 / Chapter I-3 --- Antimicrobial susceptibilities of Pseudomonas aeruginosa reported in the literature --- p.20 / Chapter II-1 --- Antibiotics and their solvents --- p.26 / Chapter II-2 --- Antibiotics and their concentrations tested --- p.27 / Chapter II-3 --- Antibiotics and their breakpoint concentration tested --- p.29 / Chapter III-1 --- Susceptibilities of 40 isolates of Salmonella sp to 12 antimicrobial agents --- p.33 / Chapter III-2 --- Susceptibilities of 40 isolates of Escherichia coli to 12 antimicrobial agents --- p.34