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 polymerirization 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.
Synthesis and biological evaluation of novel thiocolchicine-podophyllotoxin conjugates / D. Passarella, B. Peretto, R. Blasco, G. Cappelletti, D. Cartelli, C. Ronchi, J. Snaith, G. Fontana, B. Danieli, J. Borlak. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 45:1(2010 Jan), pp. 219-226. [10.1016/j.ejmech.2009.09.047]
Synthesis and biological evaluation of novel thiocolchicine-podophyllotoxin conjugates
D. Passarella;B. Peretto;G. Cappelletti;D. Cartelli;C. Ronchi;B. Danieli;
2010
Abstract
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 polymerirization 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.
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