title: Synthesis and biological evaluation of novel thiocolchicine-podophyllotoxin conjugates.
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 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.
authors.affiliation: Dipartimento di Chimica Organica e Industriale, Via Venezian 21, Università degli Studi di Milano, 20133 Milano, Italy. Daniele.Passarella@unimi.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Passarella
authors.forename: Bruno
authors.initials: B
authors.lastname: Peretto
authors.forename: Raul
authors.initials: R
authors.lastname: Blasco y Yepes
authors.forename: Graziella
authors.initials: G
authors.lastname: Cappelletti
authors.forename: Daniele
authors.initials: D
authors.lastname: Cartelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Ronchi
authors.forename: John
authors.initials: J
authors.lastname: Snaith
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fontana
authors.forename: Bruno
authors.initials: B
authors.lastname: Danieli
authors.forename: Jurgen
authors.initials: J
authors.lastname: Borlak
mesh_terms: 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
chemical_list: D014404:Tubulin; C014856:thiocholchicine; D005978:Glutathione; D011034:Podophyllotoxin; D003078:Colchicine