RESUMO
A concise and efficient synthesis of two simplified diastereomeric analogues of a natural peroxide is presented. Both compounds could be isolated in high purity and fully identified. They exhibited moderate antimalarial activity.
Assuntos
Antimaláricos/síntese química , Peróxidos/síntese química , Antimaláricos/isolamento & purificação , Peróxidos/isolamento & purificação , EstereoisomerismoRESUMO
Some perketals were synthesized by the Dussault procedure using simple bromides and 2-methoxyprop-2-yl hydroperoxide. Treatment with acetic acid gave the corresponding hydroperoxides. Both perketals and hydroperoxides were tested in vitro as trichomonacidal agents. Most of them exhibited very good activities. The most powerful compound was 2-methoxyprop-2-yl hexadec-l-yl peroxide which exhibited an IC50 value of 0.51 microM being 10 times more effective than the reference compound Metronidazole.
Assuntos
Antitricômonas/síntese química , Antitricômonas/farmacologia , Peróxidos/síntese química , Peróxidos/farmacologia , Animais , Brometos/química , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Metronidazol/farmacologia , Relação Estrutura-Atividade , Trichomonas vaginalis/efeitos dos fármacosRESUMO
Two series of three trioxanes and 18 disubstituted peroxides were synthesised and evaluated for their in vitro trichomonacidal activity against Trichomonas vaginalis. The most active compound, 2-methylprop-2-yl 2-methoxyeth-1-yl peroxide exhibited an IC(50) value of 1.0+/-0.2 microM whereas other dialkyl peroxides had various IC(50) values which could not be correlated to their molecule structure. The best compound was about five times more active than metronidazole. The amount of generated oxygen or free radicals cannot explain completely the activity suggesting another way of action for these compounds on T. vaginalis.
Assuntos
Antiprotozoários/síntese química , Peróxidos/síntese química , Trichomonas vaginalis/efeitos dos fármacos , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Radicais Livres/química , Concentração Inibidora 50 , Oxidantes/químicaRESUMO
The synthesis of 2-substituted-trifluoromethylquinolines from aniline, trifluoromethylanilines, 3-aminoquinoline and trifluoromethylquinaldines is reported. In vitro antileishmanial evaluation of 2-alkyl, 2-alkenyl and 2-epoxypropyl-trifluoromethylquinolines is presented.
Assuntos
Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Leishmania/efeitos dos fármacos , Quinolinas/síntese química , Quinolinas/farmacologia , Animais , Cromatografia em Camada Fina , Indicadores e Reagentes , Leishmania donovani/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Leishmania mexicana/efeitos dos fármacos , Espectroscopia de Ressonância MagnéticaRESUMO
Synthesis of an antileishmanial alkaloid and related compounds by using various epoxide-forming reactions is described.
Assuntos
Alcaloides/síntese química , Alcaloides/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Leishmania/efeitos dos fármacos , Animais , Compostos de Epóxi/síntese química , Compostos de Epóxi/farmacologia , Extratos Vegetais/síntese química , Extratos Vegetais/farmacologia , Plantas/química , Quinolinas/síntese química , Quinolinas/farmacologiaRESUMO
Potent antileishmanial activity has recently been described in vivo when certain 2-substituted quinoline alkaloids are administered to mice with cutaneous leishmaniasis. We now report the antileishmanial activity of four 2-substituted quinoline alkaloids, namely chimanine D or 2-(1',2'-trans-epoxypropyl) quinoline (I), 2-n-propylquinoline (II), 2-styrylquinoline (III) and 2-(2'-hydroxypropyl) quinoline (IV), for experimental treatment of visceral leishmaniasis in infected BALB/c mice. Subcutaneous treatment with chimanine D for 10 days at 0.54 mmol/kg per day resulted in 86.6% parasite suppression in the liver. Oral administration of 0.54 mmol/kg of 2-n-propylquinoline once daily for 5 or 10 days to L. donovani-infected mice suppressed parasite burdens in liver by 87.8 and 99.9%, respectively. Cutaneous administration of meglumine antimonate for 10 days resulted in 97.4% parasite suppression in the liver. This study is, to our knowledge, the first to demonstrate the activity of 2-substituted quinoline alkaloids in experimental treatment of visceral leishmaniasis. Further biological and chemical studies of these products might yet prove helpful for the development of new antileishmanial drugs.