Antimalarial activity and inhibition of monoamine oxidases A and B by exo‐erythrocytic antimalarials
- 20 April 1987
- journal article
- Published by Wiley in FEBS Letters
- Vol. 214 (2) , 291-294
- https://doi.org/10.1016/0014-5793(87)80072-8
Abstract
When the terminal amino group in the side chain of primaquine was blocked with an ethoxyacetyl group shown in 2, or eliminated by oxidative deamination to carboxylic acid 3, the antimalarial effect was markedly reduced in a screening assay which measures tissue schizonticidal activity. The optical isomers 1A and 1B of primaquine had similar antimalarial potency to the racemic mixture but 1B appeared less toxic. The 5‐phenoxy‐substituted analogue 4, belonging to a new class of antimalarials, showed similar potency in the assays to either 1A or 1B but seemed less cytotoxic than (±)‐primaquine. Compounds 1A and 1B were found to be competitive inhibitors of human monoamine oxidase (MAO) A and B (K i range 103–225 μM), but 4 showed 10–30‐fold greater competitive inhibition of MAO A (K i = 6.8 μM) and 40–90‐fold greater non‐competitive inhibition of MAO B (K i = 2.3 μM).Keywords
This publication has 11 references indexed in Scilit:
- Formation of blue diquinolinyl methine dyes by irradiation of N-acylated primaquine in chloroform solution with ultraviolet lightCanadian Journal of Chemistry, 1986
- The effects of primaquine stereoisomers and metabolites on drug metabolism in the isolated perfused rat liver and in vitro rat liver microsomesBiochemical Pharmacology, 1985
- Isolation of pure, catalytically active human liver monoamine oxidase B: Antibody complexBiochemical and Biophysical Research Communications, 1984
- Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite.British Journal of Clinical Pharmacology, 1984
- Metabolism and Distribution of Primaquine in MonkeysPharmaceutical Research, 1984
- Microbial Metabolism Studies on the Major Microbial and Mammalian Metabolite of PrimaquineJournal of Pharmaceutical Sciences, 1983
- Antimalarials. 14. 5-(Aryloxy)-4-methylprimaquine analogs. A highly effective series of blood and tissue schizonticidal agentsJournal of Medicinal Chemistry, 1982
- Modifications of primaquine as antimalarials. 3. 5-Phenoxy derivatives of primaquineJournal of Medicinal Chemistry, 1982
- Comparison of the Curative Antimalarial Activities and Toxicities of Primaquine and Its d and l IsomersAntimicrobial Agents and Chemotherapy, 1977
- The error of determination of toxicityProceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character, 1927