title: The evaluation of quinonoid compounds against Trypanosoma cruzi: synthesis of imidazolic anthraquinones, nor-beta-lapachone derivatives and beta-lapachone-based 1,2,3-triazoles.
abstract: In continuing our screening program of naphthoquinone activity against Trypanosoma cruzi, the aetiological agent of Chagas' disease, new beta-lapachone-based 1,2,3-triazoles, 3-arylamino-nor-beta-lapachones, 3-alkoxy-nor-beta-lapachones and imidazole anthraquinones were synthesised and evaluated against bloodstream trypomastigote forms of the parasite. Compounds 2,2-dimethyl-3-(2,4-dibromophenylamino)-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione, IC(50)/24h 24.9+/-7.4 and 4-azido-3-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione with 23.4+/-3.8 microM showed a trypanosomicidal activity higher than benznidazole. These results demonstrate the potential of naphthoquinone derivatives as novel structures for the development of alternative drugs for Chagas' disease.
authors.affiliation: Núcleo de Pesquisas de Produtos Naturais, UFRJ, 21941-971, Rio de Janeiro, RJ, Brazil.
authors.forename: Eufrânio N
authors.initials: EN
authors.lastname: da Silva
authors.forename: Tiago T
authors.initials: TT
authors.lastname: Guimarães
authors.forename: Rubem F S
authors.initials: RF
authors.lastname: Menna-Barreto
authors.forename: Maria do Carmo F R
authors.initials: Mdo C
authors.lastname: Pinto
authors.forename: Carlos A
authors.initials: CA
authors.lastname: de Simone
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Cavalcanti
authors.forename: José R
authors.initials: JR
authors.lastname: Sabino
authors.forename: Carlos Kleber Z
authors.initials: CK
authors.lastname: Andrade
authors.forename: Marilia O F
authors.initials: MO
authors.lastname: Goulart
authors.forename: Solange L
authors.initials: SL
authors.lastname: de Castro
authors.forename: Antônio V
authors.initials: AV
authors.lastname: Pinto
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D011809:Quinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000880:Anthraquinones; D000977:Antiparasitic Agents; D007093:Imidazoles; D009285:Naphthoquinones; D011809:Quinones; D014230:Triazoles; C014638:beta-lapachone