Cytogenetic and antineoplastic effects of modified steroidal alkylators.
Genet Test Mol Biomarkers
; 14(1): 93-7, 2010 Feb.
Article
en En
| MEDLINE
| ID: mdl-20025537
ABSTRACT
INTRODUCTION:
The aim of this study was to design new potentially antineoplastic agents by combining nitrogen mustard with steroidal skeleton, in an effort to improve specificity and simultaneously to reduce systemic toxicity. The steroidal part is aimed to act as a biological platform enabling the alkylating moiety to approach its site of action by altering its physicochemical properties. MATERIALS ANDMETHODS:
The compounds tested have, as alkylating agents, either p-N,N-bis(2-chloroethyl)aminophenyl-butyrate or p-N,N-bis(2-chloroethyl)aminophenyl-acetate esterified with a modified steroidal nucleus. The four newly synthesized compounds were compared on a molar basis, regarding their ability to induce sister chromatid exchanges and modify proliferation rate indices in cultured human lymphocytes. Life span of BDF1 mice inoculated with L1210 leukemia was also estimated (antileukemic activity).RESULTS:
A compound having p-N,N-bis(2-chloroethyl)aminophenyl-acetate as the alkylator and two ketone groups in the steroidal part demonstrated the highest statistically significant enhancement of sister chromatid exchanges and suppression of proliferation rate indices, and also caused significant antineoplastic activity. The other compounds proved less active.CONCLUSION:
These results suggest that cytogenetic and antileukemic activity of alkylating steroidal esters depends on the configuration of the whole molecule and the appropriate combination of the alkylator with the steroidal molecule.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_leukemia
Asunto principal:
Antineoplásicos Alquilantes
/
Androstanos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Genet Test Mol Biomarkers
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Grecia