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 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.
Passarella
Daniele
D
Dipartimento di Chimica Organica e Industriale, Via Venezian 21, Università degli Studi di Milano, 20133 Milano, Italy. Daniele.Passarella@unimi.it
Peretto
Bruno
B
Blasco y Yepes
Raul
R
Cappelletti
Graziella
G
Cartelli
Daniele
D
Ronchi
Cristina
C
Snaith
John
J
Fontana
Gabriele
G
Danieli
Bruno
B
Borlak
Jurgen
J
D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D011034:Podophyllotoxin / Q000737:chemistry* / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
D014404:Tubulin; C014856:thiocholchicine; D005978:Glutathione; D011034:Podophyllotoxin; D003078:Colchicine