The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil's active metabolite steroidal esters

 
see the original item page
in the repository's web site and access all digital files if the item*
share




2004 (EN)
The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil's active metabolite steroidal esters

Karayianni, V.
Mioglou-Kalouptsi, Eleftheria
Nikolaropoulos S.S.
Fousteris, M.A.
Mourelatos, D.
Arsenou, E.S.
Koutsourea, A.I.
Papageorgiou, Athanasios
Iakovidou-Kritsi, Zafeiroula

We have investigated the role of the allylic 7-ketone in oxidized Delta(5)-steroids on antileukernic activity. We synthesized and studied a series of oxidized and non-oxidized steroidal esters of p-N,N-bis(2-chloroethyl) aminophenylacetic acid (PHE), chlorambucil's active metabolite. In a comparative study of these 7-keto derivatives, on a molecular basis, regarding their ability to induce sister chromatid exchanges (SCEs) and to inhibit cell proliferation in normal human lymphocytes in vitro, the results with these 7-keto derivatives, on a molecular basis, correlated well with their antileukernic potency against leukemia P388- and L1210-bearing mice, which proved to be significantly increased compared to that of the nonoxidized derivatives. Our results indicate that the role of the steroidal skeleton it is not only for the transportation of the alkylating agent into the cell, but also contributes directly to the mechanism of antileukernic action, by an as-yet unknown way. The main conclusion from this study is that the existence of the allylic 7-keto group in the skeleton of the Delta(5)-steroidal esters impressively enhances their antileukernic activity, while the toxicity remains at clinically acceptable levels, suggesting that this structural modification should be further investigated. (C) 2004 Lippincott Williams Wilkins.

Article / Άρθρο
info:eu-repo/semantics/article

Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (EL)
Aristotle University of Thessaloniki (EN)

2004
2009-07-17T09:33:42Z


Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης, Σχολή Επιστημών Υγείας, Τμήμα Ιατρικής

Anti-Cancer Drugs, vol.15 no.10 [2004] p.983-990 [Published Version]
urn:ISSN:09594973

This record is part of 'IKEE', the Institutional Repository of Aristotle University of Thessaloniki's Library and Information Centre found at http://ikee.lib.auth.gr. Unless otherwise stated above, the record metadata were created by and belong to Aristotle University of Thessaloniki Library, Greece and are made available to the public under Creative Commons Attribution-ShareAlike 4.0 International license (http://creativecommons.org/licenses/by-sa/4.0). Unless otherwise stated in the record, the content and copyright of files and fulltext documents belong to their respective authors. Out-of-copyright content that was digitized, converted, processed, modified, etc by AUTh Library, is made available to the public under Creative Commons Attribution-ShareAlike 4.0 International license (http://creativecommons.org/licenses/by-sa/4.0). You are kindly requested to make a reference to AUTh Library and the URL of the record containing the resource whenever you make use of this material.
info:eu-repo/semantics/openAccess



*Institutions are responsible for keeping their URLs functional (digital file, item page in repository site)