title: Indolyl-3-ethanone-α-thioethers: A promising new class of non-toxic antimalarial agents.
abstract: The success of chemotherapeutics in easing the burden of malaria is under continuous threat from ever-evolving parasite resistance, including resistance to artemisinin combination therapies. Therefore, the discovery of new classes of antimalarials which inhibit new biological targets is imperative to controlling malaria. Accordingly, we report here the discovery of indolyl-3-ethanone-α-thioethers, a new class of antimalarial compounds with encouraging activity. Synthesis of a focused library of compounds revealed important insight into the SAR of this class of compounds, including critical information regarding the position and chemical nature of substituents on both the thiophenol and indole rings. This investigation ultimately led to the discovery of two hit compounds (16 and 27) which exhibited nano molar in vitro antimalarial activity coupled to no observable toxicity against a HeLa cell line.
authors.affiliation: Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa.
authors.forename: Archibald L
authors.initials: AL
authors.lastname: Svogie
authors.affiliation: Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 6140, South Africa.
authors.forename: Michelle
authors.initials: M
authors.lastname: Isaacs
authors.affiliation: Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, 6140, South Africa.
authors.forename: Heinrich C
authors.initials: HC
authors.lastname: Hoppe
authors.affiliation: Department of Chemistry, Centre for Chemico and Biomedical Research, Rhodes University, Grahamstown, 6140, South Africa.
authors.forename: Setshaba D
authors.initials: SD
authors.lastname: Khanye
authors.affiliation: Faculty of Pharmacy, Rhodes University, Grahamstown, 6140, South Africa. Electronic address: C.Veale@ru.ac.za.
authors.forename: Clinton G L
authors.initials: CG
authors.lastname: Veale
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D007211:Indoles; D013440:Sulfides; C000612959:indolyl-3-ethanone-alpha-thioether
keywords: Antimalarial; Indolyl-3-ethanone-α-thioethers; Plasmodium falciparum; Selective inhibition