Synthesis and evaluation of new oxamniquine derivatives.
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.
Filho
Silvio Barberato
SB
Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 580, CEP 05508-900 São Paulo, Brazil.
Gargioni
Cybele
C
Silva Pinto
Pedro Luiz
PL
Chiodelli
Silvia Gabriel
SG
Gurgel Vellosa
Sylvia Amaral
SA
da Silva
Rita Maria
RM
da Silveira
Maria Amélia Barata
MA
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
D012556:Schistosomicides; D010073:Oxamniquine