This work sought to characterize a link between Vitamin C and nitroglycerin at the level of enzymatic bioactivation. Before we could proceed, we needed to develop a method that sensitively and selectively identified the product of bioactivation, nitrite. We successfully adapted traditional diaminonaphthalene derivatization with the use of stable isotope...
The three dimensional structure of both a ligand and its cognate receptor are required for the success of structure-assisted drug design. This thesis reports the crystal structure of hectochlorin, a small, bioactive molecule, and the steps toward determining the crystal structure of an RNA molecule that is an attractive target...
Studies towards the total synthesis of (+)-Phomactin A (1), D (6), and G (9), fungal metabolites with unique molecular architecture and pronounced biological activity, are described. These studies resulted in the synthesis of advanced intermediates 354 and 356, which contain all of the carbon atoms of 1, 6 and 9....
The thrust of this thesis is to study oral solid dosage formulation using hot melt coating method and to use pharmacokinetic modeling and simulation (PK M&S) as a tool that can help to predict pharmacokinetics of a drug in human and the probability of passing various bioequivalence criteria of the...
Natural products have long been an important source of resources for humans. Many of these compounds possess unique chemical structures and potent biological properties. By targeting natural products with specific chemical properties, we can gain a better understanding of the roles these compounds play in the environment and their interactions...
The study of natural products (NPs) and their application has shaped humanity. Starting with the idea of using plants as medicine, it has now grown into the science of purifying and identifying organic molecules from nature to study their inherent biological activities. Understanding the molecular structures of NPs is the...
The discovery of new antibiotics reached its peak during the golden era of antibiotics in the mid 20th century and continued to thrive until the 1980s. However, after more than 50 years of fruitful exploration and exploitation of microbial natural products the discovery rate of new antibiotics has dropped drastically...
Our quest for pharmaceutically important marine natural products led to re-isolation of known mandelalides A-D and identification of new congeners E-L from re-collected South African Lissoclinum tunicate specimens. Mandelalides A, B, and L were characterized as selective cancer cell toxins, with an unusual activity profile influenced by their glycosylation /...
Despite the advance of biomedical science, infectious diseases remain one of the number one killers in the world. They claim the lives of millions of people annually, particularly in underdeveloped and developing countries. In fact, more than 32% of the health burden in Africa is caused by infectious diseases, e.g.,...
Microbial natural products represent a massive repository of unique chemical scaffolds with corresponding diverse biological functions. However, in the past decade the development of natural products into new therapeutics has dwindled, in part due to the challenges posed by high rediscovery rates and low throughput associated with classical bioassay-guided fractionation...