Synthesis of New Antimalarial Agents.
Abstract
This study is concerned with the preparation of a) peroxides based on qinghaosu, b) peptide pro-drug derivatives of primaquine, and c) thymidylate synthetase inhibitors as potentially new antimalarial agents. During the first year of this study, twelve (12) target compounds were prepared and submitted for antimalarial evaluation. An additional ten compounds were submitted during the second year of the project. The twenty-two compounds included sixteen (16) qinghaosu analogs, three (3) primaquine derivative and three (3) thymidylate synthetase inhibitors. Two peptide pro-drug derivatives or primaquine were tested for radical curvative activity against Plasmodium cynomolgi in rhesus monkeys. Eight of the qinghaosu analogs and all three of the thymidylate synthetase inhibitors were evaluated in the malaria in vitro drug screen. The qinghaosu analogs showed reasonable activity in this screen, whereas the thymidylate synthetase inhibitors were inactive. Sixteen target compounds were evaluated for blood schizonticidal suppressive activity against P. berghei in mice, and ten compounds were tested for causal prophylactic activity against P. berghei yoelii in mice. None of the compounds tested showed significant activity in these screens.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1985
- Accession Number
- ADA168171
Entities
People
- Frank I. Carroll
- John A. Kepler
Organizations
- RTI International