Synthesis and antiproliferative activity of aryl- and heteroaryl-hydrazones derived from xanthone carbaldehydes

In order to explore the antiproliferative effect associated with the xanthone framework, several arylhydrazonomethyl derivatives were synthesized from various isomeric 1,3-dihydroxyxanthone carbaldehydes. Variation in the position of the aldehydic function led to three sets of compounds, bearing the...

Full description

Saved in:
Bibliographic Details
Published in:European journal of medicinal chemistry 2008-06, Vol.43 (6), p.1336-1343
Main Authors: Varache-Lembège, Martine, Moreau, Stéphane, Larrouture, Stéphane, Montaudon, Danièle, Robert, Jacques, Nuhrich, Alain
Format: Article
Language:English
Subjects:
Aldehydes - chemical synthesis
Aldehydes - chemistry
Aldehydes - pharmacology
Antineoplastic agents
Antiproliferative activity
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation - drug effects
General aspects
Humans
Hydrazones
Hydrazones - chemical synthesis
Hydrazones - chemistry
Hydrazones - pharmacology
Magnetic Resonance Spectroscopy
Medical sciences
Pharmacology. Drug treatments
Spectrophotometry, Infrared
Xanthones
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In order to explore the antiproliferative effect associated with the xanthone framework, several arylhydrazonomethyl derivatives were synthesized from various isomeric 1,3-dihydroxyxanthone carbaldehydes. Variation in the position of the aldehydic function led to three sets of compounds, bearing the hydrazonomethyl chain at positions 5, 6 or 7 on the xanthone nucleus, respectively. The antiproliferative effect of the compounds was evaluated in vitro using the MTT colorimetric method against two human cancer cell lines (MCF-7, breast adenocarcinoma, and KB 3.1, squamous cell oral carcinoma) for two time periods (24 h and 72 h). Among the series, four compounds exhibited interesting growth inhibitory effects against both the cell lines, with IC 50 values in the micromolar concentration range. When compared with doxorubicin, the xanthone derivatives showed moderate cytotoxic effects. Surprisingly, unlike doxorubicin, these compounds displayed no significant time-dependent change in the concentration causing 50% inhibitory effect in proliferation. This unusual cytotoxicity profile led to the hypothesis that these molecules could be endowed with a mechanism of action distinct to that of doxorubicin. ▪
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2007.09.003