Synthesis and biological activity of mustard derivatives of combretastatins.
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.
Coggiola
Beatrice
B
DiSCAFF, Università del Piemonte Orientale, Via Bovio 6, 28100 Novara, Italy.
Pagliai
Francesca
F
Allegrone
Gianna
G
Genazzani
Armando A
AA
Tron
Gian Cesare
GC
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001632:Bibenzyls / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009149:Mustard Plant / Q000737:chemistry*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009584:Nitrogen / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001632:Bibenzyls; D011108:Polymers; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C040105:combretastatin; D009584:Nitrogen