Design, Synthesis and Testing of Metabolically-Stable Antimalarial Compounds
Abstract
The goal of this research is to contribute to the development of a new, more effective antimalarial drug. Malaria kills an increasing number of people each year, due in part to the ability of the parasite that causes it to develop resistance to the drugs used to treat the disease. It is therefore essential that new treatments be developed which employ novel compounds. This research is based upon one class of compounds called chalcones, which are known to kill the malaria parasite by a mechanism different from that used by existing antimalarial drugs. This means that the parasite will not have any resistance to a chalcone-based drug when it is first deployed. In this research, a series of six novel organic compounds were designed that would possess both antimalarial properties and stability in the presence of metabolizing enzymes: both requirements for a useful drug. Beginning with commercially available compounds, a four-step laboratory synthesis was devised to yield each of the novel compounds. Different chemical reactions (including nucleophilic addition, acid-hydrolysis and amide-bond formation) and purification techniques (including vacuum filtration, liquid-liquid extractions, column chromatography and thin-layer chromatography) were required. Characterization of the compounds synthesized was accomplished through Nuclear Magnetic Resonance (NMR), High Performance Liquid Chromatography Mass Spectroscopy (HPLC-MS) and Infrared Spectroscopy (IR). The six compounds produced were then tested to determine their antimalarial activity. Should the results prove promising, they will be further investigated to develop a novel antimalarial agent that treats the disease by a mechanism distinct from those used by current treatments.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2008
- Accession Number
- ADA486659
Entities
People
- Joshua W. Major
Organizations
- United States Naval Academy