RESUMO
Synthesis and antiparasitic activity vs T. cruzi and L. donovani of a series of 9-thioaryl acridines are reported. A convenient correlation between molecular structure and biological activity is proposed. Results not only agree with the classical interactions of acridines with DNA but also suggest possible role of charge transfer complexes.
Assuntos
Tripanossomicidas/síntese química , Trypanosoma/efeitos dos fármacos , Acridinas/síntese química , Acridinas/farmacologia , Animais , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Relação Quantitativa Estrutura-Atividade , Tripanossomicidas/farmacologiaRESUMO
The synthesis of several acridinic thioethers is described. Compounds prepared were tested in vitro as potential drugs against the opportunistic infection known as cryptosporidiosis. With a view to predict activity, the quantitative structure-activity relationships were investigated. Correlations between experimental data and either log P or pKa are discussed.
Assuntos
Acridinas/síntese química , Coccidiostáticos/síntese química , Cryptosporidium parvum/efeitos dos fármacos , Acridinas/farmacologia , Acridinas/uso terapêutico , Animais , Animais Recém-Nascidos , Bovinos , Linhagem Celular , Coccidiostáticos/farmacologia , Coccidiostáticos/uso terapêutico , Criptosporidiose/tratamento farmacológico , Criptosporidiose/parasitologia , Cryptosporidium parvum/crescimento & desenvolvimento , Fezes/parasitologia , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Relação Estrutura-AtividadeRESUMO
A set of 9-thioalkylacridinones, has been prepared and investigated "in vitro" against T. cruzi. Structure-antiparasitic activity relationships are detailed with a view to identify the major structural parameters for the activity under consideration.
Assuntos
Acridinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Acridinas/química , Acridinas/classificação , Animais , Antiprotozoários , Técnicas In Vitro , Camundongos , Relação Estrutura-Atividade , Tripanossomicidas/químicaRESUMO
The synthesis of 1-amino-10-alkyl-9-acridinones 4 and 5 and of homologous 9-thio-acridinones 7 and 8 are described. Similarly, the synthesis of 1-nitro-4-(2'-aminoethylamino)-9-acridinones 13 and 15, is described. Compound 4 was used as starting material for the preparation of 10-alkyl-9-acridinone dimers 6, bridged with an alpha,omega-diamido chain. Compound 15 was selected for biological investigations on pathogenic parasite strains, and a promising antiamoebic activity could be shown.
Assuntos
Acridinas/síntese química , Aminoacridinas/síntese química , Antiprotozoários/síntese química , Acanthamoeba/efeitos dos fármacos , Acridinas/farmacologia , Acridinas/toxicidade , Aminoacridinas/farmacologia , Aminoacridinas/toxicidade , Animais , Antiprotozoários/farmacologia , Antiprotozoários/toxicidade , Linfócitos T CD4-Positivos/efeitos dos fármacos , Leishmania donovani/efeitos dos fármacos , Masculino , Camundongos , Trypanosoma cruzi/efeitos dos fármacosRESUMO
New acridinonic derivatives, which are hydroxy- and methoxy-substituted in positions 1, 4, and 1,4 were prepared with a view to obtain antiparasitic drugs. These compounds were tested against Trypanosoma cruzi strains and their capability of interacalation into DNA was determined. Nucleus substitutions, DNA binding, and trypanocidal activities have been correlated.
