Synthesis and biological evaluation of paclitaxel-thiocolchicine hybrids.
The bifunctional taxoid-colchicinoid hybrids 6-8 were synthesized and evaluated in assays of cytotoxicity and tubulin assembly/disassembly. All compounds showed a high degree of cytotoxicity, but, while 6 and 7 behaved as bifunctional tubulin binders not unlike an equimolecular mixture of taxol and thiocolchicine, 8 was surprisingly devoid of tubulin activity, acting on a distinct and yet to identify molecular target.
Danieli
Bruno
B
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Venezian 21, I-20133 Milano. bruno.danieli@unimi.it
Giardini
Alessandra
A
Lesma
Giordano
G
Passarella
Daniele
D
Silvani
Alessandra
A
Appendino
Giovanni
G
Noncovich
Alain
A
Fontana
Gabriele
G
Bombardelli
Ezio
E
Sterner
Olov
O
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000138:chemical synthesis / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D017239:Paclitaxel / Q000138:chemical synthesis* / Q000494:pharmacology*
C014856:thiocholchicine; D017239:Paclitaxel; D003078:Colchicine