Novel imidazole-based combretastatin A-4 analogues: evaluation of their in vitro antitumor activity and molecular modeling study of their binding to the colchicine site of tubulin.
The in vitro antitumor activity of novel combretastatin-like 1,5- and 1,2-diaryl-1H-imidazoles was evaluated against the NCI 60 human tumor cell lines panel. Compounds 2d and 2g proved to be more cytotoxic than CA-4 in tests involving their evaluation over a 10(-4)-10(-8) range. Docking experiments showed a good correlation between the MG_MID Log GI(50) values of all these compounds and their calculated interaction energies with the colchicine binding site of alphabeta-tubulin.
Bellina
Fabio
F
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, I-56126 Pisa, Italy. bellina@dcci.unipi.it
Cauteruccio
Silvia
S
Monti
Susanna
S
Rossi
Renzo
R
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D007093:Imidazoles; D013267:Stilbenes; D014404:Tubulin; C029899:imidazole; C058728:fosbretabulin; D003078:Colchicine