Accession Number : ADB101584

Title :   Synthesis of New Antimalarial Agents.

Descriptive Note : Annual summary rept. 1 Apr 83-31 Mar 84,

Corporate Author : RESEARCH TRIANGLE INST RESEARCH TRIANGLE PARK NC

Personal Author(s) : Carroll, Frank I. ; Kepler, John A.

Report Date : MAY 1984

Pagination or Media Count : 74

Abstract : The study presented in this report is concerned with the preparation of: (a) peroxides based on qinghaosu, (b) peptide 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. The twelve compounds included eight (8) qinghaosu analogs, one (1) primaquine derivative and three (3) thymidylate synthetase inhibitors. Two 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. The primaquine peptide showed sufficient activity in the preliminary prophylactic screen to warrant its submission to the monkey P. cynomolgi screen.

Descriptors :   *ANTIMALARIALS, *SYNTHESIS(CHEMISTRY), INHIBITORS, PEPTIDES, PEROXIDES, PRIMAQUINE, SYNTHASES, SYNTHESIS, TEST AND EVALUATION, IN VITRO ANALYSIS, MONKEYS, ENZYME INHIBITORS.

Subject Categories : Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE