RESUMEN
Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Here, we have demonstrated for the first time that dillapiole has broad cytotoxic effects against a variety tumor cells. For instance, we found that it can act as a pro-oxidant compound through the induction of reactive oxygen species (ROS) release in MDA-MB-231 cells. We also demonstrated that dillapiole exhibits anti-proliferative properties, arresting cells at the G0/G1 phase and its antimigration effects can be associated with the disruption of actin filaments, which in turn can prevent tumor cell proliferation. Molecular modeling studies corroborated the biological findings and suggested that dillapiole may present a good pharmacokinetic profile, mainly because its hydrophobic character, which can facilitate its diffusion through tumor cell membranes. All these findings support the fact that dillapiole is a promising anticancer agent.
Asunto(s)
Compuestos Alílicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Dioxoles/farmacología , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Compuestos Alílicos/química , Compuestos Alílicos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Señalización del Calcio , Caspasa 3/metabolismo , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Citoesqueleto/patología , Dioxoles/química , Dioxoles/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Complejo IV de Transporte de Electrones/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Humanos , Células MCF-7 , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Simulación de Dinámica Molecular , Piper/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificaciónRESUMEN
CONTEXT: Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity. OBJECTIVE: This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy. MATERIALS AND METHODS: Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model. RESULTS: Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin. DISCUSSION AND CONCLUSION: These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.
Asunto(s)
Compuestos Alílicos/farmacología , Antiinflamatorios/farmacología , Dioxoles/farmacología , Inflamación/prevención & control , Piper , Aceites de Plantas/farmacología , Compuestos Alílicos/síntesis química , Compuestos Alílicos/aislamiento & purificación , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/aislamiento & purificación , Carragenina , Cromatografía , Dioxoles/síntesis química , Dioxoles/aislamiento & purificación , Modelos Animales de Enfermedad , Femenino , Indometacina/farmacología , Inflamación/inducido químicamente , Espectroscopía de Resonancia Magnética , Masculino , Estructura Molecular , Piper/química , Hojas de la Planta , Aceites de Plantas/química , Aceites de Plantas/aislamiento & purificación , Plantas Medicinales , Ratas , Ratas Wistar , Relación Estructura-ActividadRESUMEN
Este trabalho foi desenvolvido para análise da oxamniquina matéria-prima e para a elaboração de metodologias no controle de qualidade de suas especialidades farmacêuticas, supensão e cápsulas, especialmente em atenção à introdução da classe dos genéricos e possíveis similares. Foram realizados testes de caracterização, identificação e doseamento tanto para matéria-prima como para as formas faramcêuticas. Os resultados dos testes de caracterização mostraram-se estar de acordo com a literatura. A determinação qualitativa da oxamniquina nas amostras foi realizada por identificação de grupos funcionais da molécula e usando técnicas instrumentais. O doseamento da matéria-prima foi realizado por espectrofotometria...