Diagnosis and inhibition tools in medicinal chemistry. Part I: Synthesis and evaluation of dual wavelength fluorescent benzo[b]thiophene boronic acid derivatives for sugar sensing. Part II: Synthesis of diamidines and arylimidamides for DNA minor groove binders as antiparasitic agents.

摘要

Cell surface saccharides are involved in a variety of essential biological events. Fluorescent sensors for saccharides can be used for detection, diagnosis, analysis and monitoring of pathological processes. The boronic acid functional group is known to bind strongly and reversibly to compounds with diol groups, which are commonly found on saccharides. Sensors that have been developed for the purpose of saccharide recognition have shown great potential. However, they are very hydrophobic and this lack of essential water-solubility makes them useful in biological applications. The first section of this dissertation details the process of developing water-soluble saccharide sensors that change fluorescent properties upon binding to saccharides.;The second section of the dissertation focuses on the development of DNA-minor groove binders as antiparasitical agents. Parasitical diseases comprise some of the world's largest health problems and yet current medication and treatments for these parasitical diseases are often difficult to administer, costly to the patients, and have disruptive side effects. Worse yet, these parasites are developing drug resistance, thus creating an urgent need for new treatments. Dicationic molecules constitute a class of antimicrobial drug candidates that possess high activity against various parasites. The second section details the development of a series of dicationic agents that were then screened in in vitro activities against parasitical species.;INDEX WORDS: Boronolectins, Carbohydrate sensing, Benzo[b]thiophene boronic acid, Physiological pH, DNA-minor groove, DNA-binders, HAT, Leishmaniasis, Malaria.