title: Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners.
abstract: Malaria is a severe and life-threatening disease caused byPlasmodiumparasites that are spread to humans through bites of infectedAnophelesmosquitoes. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibitingPlasmodium falciparumparasite growth. Synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro and in mice. Benzothiophenes presented in this paper showed improved activities against a chloroquine susceptible (CQS) strain, with potencies of IC50= 6 nM, and cured 5/5Plasmodium bergheiinfected mice when dosed orally at 160 mg/kg/day × 3 days. In the benzothiophene series, the examined antiplasmodials were more active against the CQS strain D6, than against strains chloroquine resistant (CQR) W2 and multidrug-resistant (MDR) TM91C235. For the thiophene series, a very interesting feature was revealed: hypersensitivity to the CQR strains, resistance index (RI) of <1. This is in sharp contrast to chloroquine, indicating that further development of the series would provide us with more potent antimalarials against CQR strains.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 51, 11158 Belgrade, Serbia. jelena_konstantinovic@chem.bg.ac.rs.
authors.forename: Jelena
authors.initials: J
authors.lastname: Konstantinović
authors.affiliation: Innovation Center of the Faculty of Chemistry, Studentski trg 12-16, 11158 Belgrade, Serbia. milica_videnovic@chem.bg.ac.rs.
authors.forename: Milica
authors.initials: M
authors.lastname: Videnović
authors.affiliation: Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia. jelena.srbljanovic@imi.bg.ac.rs.
authors.forename: Jelena
authors.initials: J
authors.lastname: Srbljanović
authors.affiliation: Institute for Medical Research, University of Belgrade, Dr. Subotića 4, 11129 Belgrade, Serbia. olgicadj@imi.bg.ac.rs.
authors.forename: Olgica
authors.initials: O
authors.lastname: Djurković-Djaković
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 51, 11158 Belgrade, Serbia. bogojevickatarina@gmail.com.
authors.forename: Katarina
authors.initials: K
authors.lastname: Bogojević
authors.affiliation: Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. richard.j.sciotti.civ@mail.mil.
authors.forename: Richard
authors.initials: R
authors.lastname: Sciotti
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 51, 11158 Belgrade, Serbia. bsolaja@chem.bg.ac.rs.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Šolaja
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D018432:Drug Resistance, Multiple / Q000187:drug effects; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D013876:Thiophenes / Q000737:chemistry*
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D013876:Thiophenes; C088015:benzothiophene
keywords: aminoquinoline; antimalarials; benzothiophene; thiophene