fosbretabulin and Neuroblastoma

We have synthesized rigid analogues of combretastatin bearing a furan ring in place of the olefinic bridge. These compounds are cytotoxic at nanomolar concentrations in neuroblastoma cells, display a similar structure-activity relationship compared to combretastatin A4, and inhibit tubulin polymerization. We also show that the furan ring can be further functionalized. Thus, it is possible that combretafurans could act as scaffolds for the development of dual-action antitumoral agents.

Topics: Anisoles; Antineoplastic Agents; Bibenzyls; Cell Death; Cell Line, Tumor; Drug Screening Assays, Antitumor; Furans; Humans; Molecular Structure; Neuroblastoma; Stilbenes; Structure-Activity Relationship; Tubulin

A series of chimeric compounds bearing the combretastatin and the nitrogen mustard cores were synthesized. All the compounds were cytotoxic and inhibited tubulin polymerization. When combretastatin was joined to chlorambucil via an ester linkage, the resultant compound proved to be significantly more potent than the two compounds put together. When combretastatin was joined to nitrogen mustard via an ether linkage or when a true hybrid was synthesized, loss of potency was observed. Nonetheless, these latter compounds appeared to be more efficacious and surprisingly were able to inhibit tubulin depolymerization at high concentrations.

Topics: Antineoplastic Agents; Bibenzyls; Humans; Inhibitory Concentration 50; Mustard Plant; Neuroblastoma; Nitrogen; Polymers; Stilbenes; Structure-Activity Relationship; Tubulin; Tubulin Modulators; Tumor Cells, Cultured