New 7-aryl analogues of anthracyclines: Synthesis and cytotoxic activity of (±)-7-(3,4,5-trimethoxyphenyl)-7-deoxyidarubicinone

The synthetic methodology for the preparation of 7-aryl-7-deoxyanthracyclinones, a new class of anthracycline analogues, is described. Readily available materials are easily transformed into the key intermediate ketone, that is converted into bent and planar tetracyclic compounds. Cytotoxic studies...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1997-12, Vol.7 (23), p.2955-2958
Main Authors: Acosta, J.C., Caballero, E., Grávalos, D.Ga, Medarde, M., Sahagún, H., Stoodley, R.J., Tomé, F.
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Medical sciences
Miscellaneous. Antibiotics with multiple activities
Pharmacology. Drug treatments
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Summary:The synthetic methodology for the preparation of 7-aryl-7-deoxyanthracyclinones, a new class of anthracycline analogues, is described. Readily available materials are easily transformed into the key intermediate ketone, that is converted into bent and planar tetracyclic compounds. Cytotoxic studies of the final and intermediate products reveal a moderate activity of bent products and a lack of activity of planar products, thus supporting a non-intercalating mechanism for their cytotoxic activity. Bent and planar 7-aryl-7-deoxy analogues of idarubicinone are synthesized from readily available materials. A non-intercalating mode of action is suggested, due to the higher cytotoxicity of bent tetracyclic compounds.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(97)10122-6