RESUMEN
Chicken coccidiosis is a major parasitic disease caused by Eimeria spp. It is controlled and treated using chemical anticoccidial agents. Development of partial or complete resistance toward these anticoccidials is considered a major problem in poultry industry. Allicin is an organosulfur compound produced as a result of the reaction between alliin and alliinase after hacking of garlic. In this study, tenfold dilution from 180 mg/ml to 1.8 ng/ml of allicin in distilled water was tested against E. tenella in vitro. The percent of inhibition in allicin was from 99.9 to 71.53% using 180 mg/ml and 180 ng/ml, respectively. The percent of inhibition was 56.24% using 1.8 ng/ml. We used allicin as a treatment from plants against chicken coccidiosis; however, in vivo study should be performed to confirm these results.
Asunto(s)
Coccidiosis/tratamiento farmacológico , Coccidiostáticos/administración & dosificación , Eimeria tenella/efectos de los fármacos , Ajo/química , Extractos Vegetales/administración & dosificación , Enfermedades de las Aves de Corral/tratamiento farmacológico , Ácidos Sulfínicos/administración & dosificación , Animales , Pollos/parasitología , Coccidiosis/parasitología , Disulfuros , Eimeria tenella/crecimiento & desarrollo , Enfermedades de las Aves de Corral/parasitología , Esporozoítos/efectos de los fármacos , Esporozoítos/crecimiento & desarrolloRESUMEN
Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration < 1 micromolar) and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open-source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.
Asunto(s)
Antimaláricos/farmacología , Descubrimiento de Drogas , Imidazoles/farmacología , Hígado/parasitología , Malaria/tratamiento farmacológico , Piperazinas/farmacología , Plasmodium/efectos de los fármacos , Animales , Antimaláricos/química , Antimaláricos/farmacocinética , Antimaláricos/uso terapéutico , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Resistencia a Medicamentos , Eritrocitos/parasitología , Humanos , Imidazoles/química , Imidazoles/farmacocinética , Imidazoles/uso terapéutico , Malaria/parasitología , Malaria/prevención & control , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Piperazinas/química , Piperazinas/farmacocinética , Piperazinas/uso terapéutico , Plasmodium/citología , Plasmodium/crecimiento & desarrollo , Plasmodium/fisiología , Plasmodium berghei/citología , Plasmodium berghei/efectos de los fármacos , Plasmodium berghei/crecimiento & desarrollo , Plasmodium berghei/fisiología , Plasmodium falciparum/citología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/fisiología , Plasmodium yoelii/citología , Plasmodium yoelii/efectos de los fármacos , Plasmodium yoelii/crecimiento & desarrollo , Plasmodium yoelii/fisiología , Polimorfismo de Nucleótido Simple , Proteínas Protozoarias/química , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Distribución Aleatoria , Bibliotecas de Moléculas Pequeñas , Esporozoítos/efectos de los fármacos , Esporozoítos/crecimiento & desarrolloRESUMEN
Most medicinal plants used against malaria in endemic areas aim to treat the acute symptoms of the disease such as high temperature fevers with periodicity and chills. In some endemic areas of the Brazilian Amazon region one medicinal plant seems to be an exception: Ampelozyziphus amazonicus, locally named "Indian beer" or "Saracura-mira", used to prevent the disease when taken daily as a cold suspension of powdered dried roots. In previous work we found no activity of the plant extracts against malaria blood parasites in experimentally infected animals (mice and chickens) or in cultures of Plasmodium falciparum. However, in infections induced by sporozoites, chickens treated with plant extracts were partially protected against Plasmodium gallinaceum and showed reduced numbers of exoerythrocytic forms in the brain. We now present stronger evidence that the ethanolic extract of "Indian beer" roots hampers in vitro and in vivo development of Plasmodium berghei sporozoites, a rodent malaria parasite. Some mice treated with high doses of the plant extract did not become infected after sporozoite inoculation, whereas others had a delayed prepatent period and lower parasitemia. Our data validates the use of "Indian beer" as a remedy for malaria prophylaxis in the Amazon, where the plant exists and the disease represents an important problem which is difficult to control. Studies aiming to identify the active compounds responsible for the herein described causal prophylactic activity are needed and may lead to a new antimalarial prophylactic.