SYNTHESIS AND BIOLOGICAL EVALUATION OF NATURE-INSPIRED N-HYDROXYPYRIDONES AND THEIR DERIVATIVES

Abstract

Malaria is an infectious disease causing deaths of thousands of children. The eradication of malaria remains as a big challenge in the world. N-hydroxypyridone natural products have been reported to display a range if biological activities, including anti-malarial properties. However, the total synthesis of naturally occurring N-hydroxypyridones and the full scope of the biological activities of these compounds remain largely unexplored. This project commenced with the total synthesis of cordypyridones and pyridoxatin. Four synthetic routes were thoroughly investigated and a novel methodology was developed. Two libraries of N-hydroxypyridones were synthesized. The anti-plasmodial, anti-bacterial and anti-oxidant activities of these two libraries of compounds were evaluated. Three compounds were identified as leads. An iron chelation study was also conducted to evaluate the properties of N-hydroxy-2-pyridone motif. The results showed that compounds with N-hydroxy-2-pyridone motif are good iron chelators as compared with EDTA.