Synthesis and biological evaluation of novel thiocolchicine–podophyllotoxin conjugates

The synthesis and biological evaluation of 9 dimeric compounds obtained by condensation of thiocolchicine and/or podophyllotoxin with 6 different dicarboxylic acids is described. In particular, tubulin assembly assay and immunofluorescence analysis results are reported. The biological data highlight...

Full description

Saved in:
Bibliographic Details
Published in:European journal of medicinal chemistry 2010, Vol.45 (1), p.219-226
Main Authors: Passarella, Daniele, Peretto, Bruno, Blasco y Yepes, Raul, Cappelletti, Graziella, Cartelli, Daniele, Ronchi, Cristina, Snaith, John, Fontana, Gabriele, Danieli, Bruno, Borlak, Jurgen
Format: Article
Language:English
Subjects:
Animals
Anticancer drugs
Antineoplastic agents
Biological and medical sciences
Cattle
Cell Line, Tumor
Colchicine - analogs & derivatives
Colchicine - chemistry
Colchicine - pharmacology
Fluorescent Antibody Technique
General aspects
Glutathione - metabolism
Humans
Inhibitory Concentration 50
Medical sciences
Mice
Microtubule network
Pharmacology. Drug treatments
Podophyllotoxin
Podophyllotoxin - chemistry
Podophyllotoxin - pharmacology
Protein Multimerization - drug effects
Protein Structure, Quaternary
Thiocolchicine
Tubulin - chemistry
Tubulin - metabolism
Tubulin polymerization
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:The synthesis and biological evaluation of 9 dimeric compounds obtained by condensation of thiocolchicine and/or podophyllotoxin with 6 different dicarboxylic acids is described. In particular, tubulin assembly assay and immunofluorescence analysis results are reported. The biological data highlighted three compounds as being more active than the others, having a marked ability to inhibit the polymerization of tubulin in vitro and causing significant disruption to the microtubule network in vivo. The spacer unit was found to have a significant effect on biological activity, reinforcing the importance of the design of conjugate compounds to create new biologically active molecules in which the spacer could be useful to improve the solubility and to modulate the efficacy of well known anticancer drugs. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2009.09.047