title: Synthesis of novel triazole-linked mefloquine derivatives: biological evaluation against Plasmodium falciparum.
abstract: Using 2,8-bis(trifluoromethyl)quinoline, the pharmacophore of mefloquine, as scaffold, eleven novel triazole-linked compounds have been synthesised by the application of CuAAC chemistry. The in vitro biological activity of the compounds on the Plasmodium falciparum chloroquine-sensitive strain NF54 was then determined. The compounds all showed IC50s in the lower μM range with (1R,3S,5R)-N-{[1-(2,8-bis(trifluoromethyl)quinoline-4-yl)-1H-1,2,3-triazol-4-yl]methyl}adamantan-2-amine (29) exhibiting the best activity of 1.00 μM.
authors.affiliation: Department of Chemistry and Polymer Science, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
authors.forename: Anton R
authors.initials: AR
authors.lastname: Hamann
authors.affiliation: Department of Pharmacology, University of Cape Town, Groote Schuur Hospital, South Africa.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Kock
authors.affiliation: Department of Pharmacology, University of Cape Town, Groote Schuur Hospital, South Africa.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Polymer Science, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
authors.forename: Willem A L
authors.initials: WA
authors.lastname: van Otterlo
authors.affiliation: Department of Chemistry and Polymer Science, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa.
authors.forename: Margaret A L
authors.initials: MA
authors.lastname: Blackie
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D015767:Mefloquine / Q000008:administration & dosage / Q000627:therapeutic use*; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D014230:Triazoles; D015767:Mefloquine
keywords: 1,2,3-Triazole; 2,8-Bis(trifluoromethyl)quinoline; CuAAC chemistry; P. falciparum