A series of novel hybrid compounds obtained by the attachment of anhydrovinblastine, vinorelbine, and vindoline to thiocolchicine, podophyllotoxin, and baccatin III are described. Two types of diacyl spacers are introduced. The influence of the hybrid compounds on tubulin polymerization is reported. The results highlight the importance of the length of the spacer. Immunofluorescence microscopy and flow cytometry measurements that compound with the best in vitro activity could disrupt microtubule networks in cell and prevent the formation of the proper spindle apparatus, thereby causing cell cycle arrest in the G2/M phase. The newly synthesized compounds were tested in the human lung cancer cell line A549.

Inhibitors of tubulin polymerization: synthesis and biological evaluation of hybrids of vindoline, anhydrovinblastine and vinorelbine with thicolchicine, podophyllotoxin and baccatin III / D. Passarella, A. Giardini, B. Peretto, G. Fontana, A. Sacchetti, A. Silvani, C. Ronchi, G. Cappelletti, D. Cartelli, J. Borlak, B. Danieli. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 16:11(2008 Jun 01), pp. 6269-6285.

Inhibitors of tubulin polymerization: synthesis and biological evaluation of hybrids of vindoline, anhydrovinblastine and vinorelbine with thicolchicine, podophyllotoxin and baccatin III

D. Passarella;A. Giardini;B. Peretto;A. Sacchetti;A. Silvani;C. Ronchi;G. Cappelletti;D. Cartelli;B. Danieli
2008

Abstract

A series of novel hybrid compounds obtained by the attachment of anhydrovinblastine, vinorelbine, and vindoline to thiocolchicine, podophyllotoxin, and baccatin III are described. Two types of diacyl spacers are introduced. The influence of the hybrid compounds on tubulin polymerization is reported. The results highlight the importance of the length of the spacer. Immunofluorescence microscopy and flow cytometry measurements that compound with the best in vitro activity could disrupt microtubule networks in cell and prevent the formation of the proper spindle apparatus, thereby causing cell cycle arrest in the G2/M phase. The newly synthesized compounds were tested in the human lung cancer cell line A549.
Bivalent inhibitors; Tubulin polymerization; Vinca alkaloids
Settore BIO/06 - Anatomia Comparata e Citologia
Settore CHIM/06 - Chimica Organica
1-giu-2008
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/53938
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