title: Preparation and antimalarial activity of a novel class of carbohydrate-derived, fused thiochromans.
abstract: A novel class of fused thiochroman derivatives has been prepared by an efficient and versatile synthetic procedure involving nucleophilic displacement of the side-chain iodo substituent in 2-deoxy-2-C-iodomethyl glucosides by thiophenolate ions, and subsequent intramolecular C-glycoside formation. A range of aromatic substituents is tolerated, and the subsequent facile selective oxidation of the sulfur to the sulfoxide or sulfone level expands the range and molecular diversity of the series of compounds. A selection of the sulfoxide and sulfone derivatives bearing lipophilic substituents on the aromatic portion were found to have antimalarial activities in the low micromolar range.
authors.affiliation: Department of Chemistry, University of Johannesburg, Auckland Park 2006, South Africa. Electronic address: hhkinfe@uj.ac.za.
authors.forename: Henok H
authors.initials: HH
authors.lastname: Kinfe
authors.affiliation: Department of Chemistry, University of Johannesburg, Auckland Park 2006, South Africa.
authors.forename: Paseka T
authors.initials: PT
authors.lastname: Moshapo
authors.affiliation: Department of Chemistry, University of Johannesburg, Auckland Park 2006, South Africa.
authors.forename: Felix L
authors.initials: FL
authors.lastname: Makolo
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: David W
authors.initials: DW
authors.lastname: Gammon
authors.affiliation: Institute of Organic Chemistry, University of Duisburg-Essen, Universitätstrasse 7, 45141 Essen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Ehlers
authors.affiliation: Institute of Organic Chemistry, University of Duisburg-Essen, Universitätstrasse 7, 45141 Essen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmuck
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000138:chemical synthesis* / Q000494:pharmacology*; D006027:Glycosides; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D015394:Molecular Structure; D009005:Monosaccharides / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry
chemical_list: D000962:Antimalarials; C438934:C-glycoside; D002241:Carbohydrates; D002839:Chromans; D006027:Glycosides; D009005:Monosaccharides; D013450:Sulfones
keywords: Antimalarial; Chloroquine-resistant; Chloroquine-sensitive; Thiochromans