title: 1,2,4-Triazino-[5,6b]indole derivatives: effects of the trifluoromethyl group on in vitro antimalarial activity.
abstract: In an attempt to search for new and alternative antimalarial agents, a series of unsubstituted and 6-trifluoromethyl-1,2,4-triazino[5,6b]indole and 5H-1,2,4-triazolo[1',5',2,3]-1,2,4-triazino[5,6b]indole derivatives were synthesized and their chemical structures confirmed by 1H NMR and 13C NMR, elemental, IR and mass spectrophotometric analyses. The in vitro antimalarial activities of these compounds were evaluated against the chloroquine-sensitive (D10) and the chloroquine-resistant (RSA11) strains of Plasmodium falciparum. The 1,2,4-triazino[5,6b]indole derivatives (4, 6 and 8) with a trifluoromethyl group at position 6 exhibit increased in vitro activity when compared to the unsubstituted analogues, which are all devoid of activity. The presence of the trifluoromethyl group in the 5H-1,2,4-triazolo[1',5',2,3]-1,2,4-triazino[5,6b]indole ring system leads to compounds with diminished antimalarial activity when compared to the corresponding unsubstituted analogues. The compounds associate with ferriprotoporphyrin IX and interact with DNA to more or less the same extent.
authors.affiliation: Medicine Control Council, Department of Health, Private Bag X828, Pretoria 0001, South Africa.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kgokong
authors.forename: Peter P
authors.initials: PP
authors.lastname: Smith
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Matsabisa
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D006427:Hemin / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D007211:Indoles; D006427:Hemin; D002738:Chloroquine; D004247:DNA; D007770:L-Lactate Dehydrogenase