title: Synthesis and evaluation of new oxamniquine derivatives.
abstract: Oxamniquine derivatives were synthesized and evaluated as novel schistosomicide agents. Oxamniquine (1,2,3,4-tetrahydro-2-[[(1-methylethyl)amino]methyl]-7-nitro-6-quinolinemethanol) was submitted to the Mannich reaction, using formaldehyde, paraformaldehyde and acetaldehyde as reagents, and gave three unexpected products: two of them were cyclized on the alkylamine side chain and another etherified on the aminequinolinemethanol group. The three compounds were biologically evaluated using mice infected with Schistosoma mansoni and showed promising activities, but had higher toxicities. For studies on structure-activity relationships, results demonstrate that the side alkylamine group can be modified with preserved activity, but that this modification is associated with increased toxicity.
authors.affiliation: Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 580, CEP 05508-900 São Paulo, Brazil.
authors.forename: Silvio Barberato
authors.initials: SB
authors.lastname: Filho
authors.forename: Cybele
authors.initials: C
authors.lastname: Gargioni
authors.forename: Pedro Luiz
authors.initials: PL
authors.lastname: Silva Pinto
authors.forename: Silvia Gabriel
authors.initials: SG
authors.lastname: Chiodelli
authors.forename: Sylvia Amaral
authors.initials: SA
authors.lastname: Gurgel Vellosa
authors.forename: Rita Maria
authors.initials: RM
authors.lastname: da Silva
authors.forename: Maria Amélia Barata
authors.initials: MA
authors.lastname: da Silveira
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008297:Male; D051379:Mice; D010073:Oxamniquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000627:therapeutic use; D012555:Schistosomiasis mansoni / Q000188:drug therapy; D012556:Schistosomicides / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D012556:Schistosomicides; D010073:Oxamniquine