Cytogenetic and Antineoplastic Effects of Modified Steroidal Alkylators
| Autor: | Sotiris S. Nikolaropoulos, George Pairas, Manolis A. Fousteris, Denis Mourelatos, T. Lialiaris, Anna I. Koutsourea, Irini Karapidaki, George D. Geromichalos, Athanasios A. Papageorgiou, Ioanna Papaconstadinou |
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| Rok vydání: | 2010 |
| Předmět: |
Ketone
In Vitro Techniques Biology Mice chemistry.chemical_compound Proliferation rate Animals Humans Moiety Sister chromatids Lymphocytes Leukemia L1210 Antineoplastic Agents Alkylating Cells Cultured Genetics (clinical) Cell Proliferation chemistry.chemical_classification Molecular Structure General Medicine Nitrogen mustard Systemic toxicity chemistry Biochemistry Drug Design Drug Screening Assays Antitumor Sister Chromatid Exchange Site of action Androstanes |
| Zdroj: | Genetic Testing and Molecular Biomarkers. 14:93-97 |
| ISSN: | 1945-0257 1945-0265 |
| DOI: | 10.1089/gtmb.2009.0059 |
| Popis: | 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.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).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.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. |
| Databáze: | OpenAIRE |
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