Synthetic peroxides as antimalarials: Identification of a secondary ozonide (1,2,4-trioxolane) drug development candidate

MEDI 2

Jonathan L Vennerstrom, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025
The discovery of artemisinin in 1971 initiated a new era in malaria chemotherapy. Although the clinically useful semisynthetic artemisinin derivatives are rapid acting and potent antimalarial drugs, they have short half-lives and must be administered over a period of 5-7 days, leading to noncompliance and recrudescence. With this in view, many synthetic peroxide antimalarials have been prepared. Yet, identification of synthetic peroxides that are easily synthesized, inexpensive, and with good biopharmaceutical properties has been surprisingly difficult. In this seminar, we document the pitfalls and progress made in this endeavor, and highlight the discovery of a secondary ozonide (1,2,4-trioxolane) drug development candidate.