title: Synthesis and anti-Trypanosoma cruzi activity of new 3-phenylthio-nor-β-lapachone derivatives.
abstract: We report herein a straightforward and efficient one-step reaction to prepare new nor-β-lapachone derivatives tethered with phenylthio groups at position 3 of the furan ring. We have screened the compounds on bloodstream trypomastigotes of Trypanosoma cruzi, the causative agent of Chagas disease, aimed at finding a new prototype with high trypanocidal activity. The new compounds possess a broad range of activity (IC50/24h from 9.2 to 182.7 μM), higher than the original quinone (391.5 μM) and four of them higher than standard drug benznidazole (103.6 μM). The most active was compound 13b (9.2 μM), being 11 times active than benznidazole and the less toxic derivative to heart muscle cells.
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, 24020-150 Niterói, RJ, Brazil.
authors.forename: Mariana F do Carmo
authors.initials: MFDC
authors.lastname: Cardoso
authors.affiliation: Laboratório de Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Kelly
authors.initials: K
authors.lastname: Salomão
authors.affiliation: Laboratório de Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Bombaça
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, 24020-150 Niterói, RJ, Brazil.
authors.forename: David R
authors.initials: DR
authors.lastname: da Rocha
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, 24020-150 Niterói, RJ, Brazil.
authors.forename: Fernando de C
authors.initials: FC
authors.lastname: da Silva
authors.affiliation: Department of Chemistry and QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: José A S
authors.initials: JAS
authors.lastname: Cavaleiro
authors.affiliation: Laboratório de Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21045-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Solange L
authors.initials: SL
authors.lastname: de Castro
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, 24020-150 Niterói, RJ, Brazil. Electronic address: cegvito@vm.uff.br.
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D014355:Chagas Disease / Q000188:drug therapy; D004622:Embryo, Mammalian / Q000166:cytology; D006321:Heart / Q000187:drug effects; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009285:Naphthoquinones / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D001572:Benzofurans; D009285:Naphthoquinones; D014344:Trypanocidal Agents; C574726:nor-beta-lapachone
keywords: Chagas disease; Naphthoquinone; Nor-β-lapachone; Thiol derivative; Trypanosoma cruzi