RESUMEN
7 alpha-, 17 alpha-Diaza-7, 17-dioxo-B, D-dihomo-5-androsten 3 beta-p-N, N-bis (2- chloroethyl)aminophenylacetate, a modified steroidal alkylating agent, is active in the treatment of P388 and L1210 leukemias in vivo. The compound was also tested in vitro against L1210 and P388 leukemias, on DNA, RNA and protein synthesis and showed high inhibition effect. Also increases the frequency of Sister Chromatid Exchanges and reduces the replication index of human lymphocytes.
Asunto(s)
Antineoplásicos/toxicidad , Antineoplásicos/uso terapéutico , Compuestos Aza/toxicidad , Compuestos Aza/uso terapéutico , Azaesteroides , Homoesteroides/toxicidad , Homoesteroides/uso terapéutico , Leucemia L1210/tratamiento farmacológico , Leucemia P388/tratamiento farmacológico , Intercambio de Cromátides Hermanas/efectos de los fármacos , Animales , Compuestos Aza/síntesis química , División Celular/efectos de los fármacos , Células Cultivadas , Femenino , Homoesteroides/síntesis química , Humanos , Indicadores y Reactivos , Linfocitos/citología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Ratones Endogámicos , Estructura Molecular , Células Tumorales CultivadasRESUMEN
The homo-aza-steroidal esters of conjugated carboxylic derivatives of nitrogen mustards are reviewed. Particularly we discuss the antitumor activity of cinnamic acid and benzoic acid mustard isomers, esters of homo-aza-steroids in which the mustard acid is linked to the C-3 or C17 position, while the lactam nucleus is in the D or A ring of the steroid respectively. The current literature indicates that the potential is due to the synergistic activity of both the steroidal lactam and the mustard of the acids. Steroidal lactams, namely 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, the isomer 3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic- 13,17-lactam, 3 beta-hydroxy-13 alpha-amino 13,17-seco-5-androsten-17-oic-13,17-lactam and the 17 beta-hydroxy-3-aza-A-homo- 4 alpha-androsten-4-one, have been used as biological platforms of the cinnamic acid, of the benzoic acid mustard isomers and the 4-methyl-benzoic acid mustard. The twelve esters of cinnamic acid mustard isomers were tested against P388, L1210 leukemias Ehrlich ascites tumor (EAT) and melanoma B16 in vivo. The effect of homo-aza-steroidal esters of N,N-bis(2-chloroethyl) amino cinnamic acid isomers on the incorporation of the radioactive precursors into DNA, RNA and proteins of L1210, P388 leukemias, Ehrlich ascites tumor (EAT) and Baby Hamster Kidney (BHK) cells, was investigated. The effect of the homo-aza-steroidal esters of N,N-bis(2-chloroethyl) aminobenzoic acid isomers on the incorporation of radioactive precursors into DNA, RNA and proteins was studied in L1210, P388 leukemias, Ehrlich ascites tumor and Baby hamster kidney cells.
Asunto(s)
Antineoplásicos/uso terapéutico , Azaesteroides/uso terapéutico , Homoesteroides/uso terapéutico , Compuestos de Mostaza Nitrogenada/uso terapéutico , Animales , Antineoplásicos/toxicidad , Azaesteroides/química , Azaesteroides/toxicidad , Carcinoma de Ehrlich/tratamiento farmacológico , Carcinoma de Ehrlich/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cricetinae , ADN de Neoplasias/biosíntesis , ADN de Neoplasias/efectos de los fármacos , Homoesteroides/química , Homoesteroides/toxicidad , Riñón , Leucemia L1210/tratamiento farmacológico , Leucemia L1210/metabolismo , Leucemia P388/tratamiento farmacológico , Leucemia P388/metabolismo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Ratones , Estructura Molecular , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/efectos de los fármacos , Compuestos de Mostaza Nitrogenada/química , Compuestos de Mostaza Nitrogenada/toxicidad , ARN Neoplásico/biosíntesis , ARN Neoplásico/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
A new sesterterpene, 12-deacetoxyscalaradial [2a] has been isolated from the sponge Cacospongia mollior, together with the previously described scalaradial [2b] and furoscalarol [3]. The structure of the new compound, proposed by spectral data, was confirmed by X-ray diffraction analysis. Compound 2a is the first scalarane sesterterpenoid, without a substituent at C-12, to have been identified in nature. It shows high antifeedant activity and is hot to taste for the human tongue. Both 2a and 2b display cytotoxic activity.