title: On the search for potential anti-Trypanosoma cruzi drugs: synthesis and biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic naphthoquinoidal compounds obtained by click chemistry reactions.
abstract: Five 2-hydroxy-3-substituted-aminomethyl naphthoquinones, nine 1,2,3-triazolic para-naphthoquinones, five nor-β-lapachone-based 1,2,3-triazoles, and several other naphthoquinonoid compounds were synthesized and evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease, continuing our screening program for new trypanocidal compounds. Among all the substances, 16-18, 23, 25-29 and 30-33 were herein described for the first time and fifteen substances were identified as more potent than the standard drug benznidazole, with IC(50)/24h values in the range of 10.9-101.5 μM. Compounds 14 and 19 with Selectivity Index of 18.9 and 6.1 are important structures for further studies.
authors.affiliation: Laboratório de Química Sintética e Heterocíclica, Instituto de Ciências Exatas, Departamento de Química, Av. Antônio Carlos, 6627 Pampulha, UFMG, 31270-901 Belo Horizonte, MG, Brazil. eufranio@ufmg.br
authors.forename: Eufrânio N
authors.initials: EN
authors.lastname: da Silva Júnior
authors.forename: Isadora M M
authors.initials: IM
authors.lastname: de Melo
authors.forename: Emilay B T
authors.initials: EB
authors.lastname: Diogo
authors.forename: Verenice A
authors.initials: VA
authors.lastname: Costa
authors.forename: José D
authors.initials: JD
authors.lastname: de Souza Filho
authors.forename: Wagner O
authors.initials: WO
authors.lastname: Valença
authors.forename: Celso A
authors.initials: CA
authors.lastname: Camara
authors.forename: Ronaldo N
authors.initials: RN
authors.lastname: de Oliveira
authors.forename: Alexandre S
authors.initials: AS
authors.lastname: de Araujo
authors.forename: Flávio S
authors.initials: FS
authors.lastname: Emery
authors.forename: Marcelo R
authors.initials: MR
authors.lastname: dos Santos
authors.forename: Carlos A
authors.initials: CA
authors.lastname: de Simone
authors.forename: Rubem F S
authors.initials: RF
authors.lastname: Menna-Barreto
authors.forename: Solange L
authors.initials: SL
authors.lastname: de Castro
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry; D055808:Drug Discovery; D051379:Mice; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014230:Triazoles / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D009285:Naphthoquinones; D014230:Triazoles; D014344:Trypanocidal Agents