RESUMEN
Cortiphen, a newly developed hormonal cytostatic ester of 11-desoxy-17 alpha-hydroxycorticosterone and chlorophenacyl, is described. It was studied in transplantable, spontaneous and induced tumors of 7 sites: hemoblastosis (5), hepatoma (3), mammary gland (5), lung (2), gastrointestinal tract (3), sarcoma (2) and melanoma. Practically all the tumors were shown to respond to cortiphen action. Among the antitumor effects of the drug were: long-term inhibition of tumor growth or tumor regression, contribution to longer survival, antimetastatic action and sustained action during repeated courses of administration. Cortiphen was found to interact with glucocorticoid receptors in both animal and human tumors. The role of the hormonal component of the drug's molecule in the realization of its antitumor effect is discussed.
Asunto(s)
Corticosterona/análogos & derivados , Compuestos de Mostaza Nitrogenada/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Corticosterona/farmacocinética , Corticosterona/farmacología , Corticosterona/uso terapéutico , Corticosterona/toxicidad , Perros , Combinación de Medicamentos/farmacocinética , Combinación de Medicamentos/farmacología , Combinación de Medicamentos/uso terapéutico , Combinación de Medicamentos/toxicidad , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos , Trasplante de Neoplasias , Neoplasias/metabolismo , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Compuestos de Mostaza Nitrogenada/farmacocinética , Compuestos de Mostaza Nitrogenada/farmacología , Compuestos de Mostaza Nitrogenada/toxicidad , Ratas , Receptores de Glucocorticoides/efectos de los fármacos , Receptores de Glucocorticoides/metabolismoRESUMEN
A number of derivatives of 2-amino-2-deoxysaccharides and 1-methylamino-1-deoxypolyols acylated by cytotoxic phenylalkanic and amino acids were synthesized and experimentally tested for antitumor activity. Some compounds showed a high antitumor activity against plasmacytoma MOPC-406: a 2-fold increase in experimental animals survival and a 80--100% cure rate were observed. Physicochemical properties, particularly, stability in aqueous solution and antitumor activity of one of the most potent compounds--1-methylamino-1-deoxy-1-N[p-di(2-chloroethyl) aminophenylacetyl]-D-glucitol (Agluphen)--are described in detail.