Diarylmethyloxime and hydrazone derivatives with 5-indolyl moieties as potent inhibitors of tubulin polymerization.
We describe the synthesis and biological evaluation of a series of diarylmethyloxime and diarylmethylhydrazone analogues that contain an indole ring and different modifications on the nitrogen of the bridge. Several compounds showed potent tubulin polymerization inhibitory action as well as cytotoxic activity against cancer cell lines. The N-methyl-5-indolyl substituted analogues are more potent than ethyl substituted ones. The most potent inhibitors of tubulin polymerization are the diarylketones and the diaryloximes. The cytotoxicity against several cancer cell lines is lower for the oximes than for the ketones. Other substitutions on the imine nitrogen greatly reduce the tubulin inhibitory and/or cytotoxic potencies.
Alvarez
Concepción
C
Departament de Química Farmacéutica, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Alvarez
Raquel
R
Corchete
Purificación
P
López
José Luis
JL
Pérez-Melero
Concepción
C
Peláez
Rafael
R
Medarde
Manuel
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000633:toxicity; D001577:Benzophenones / Q000737:chemistry; D001632:Bibenzyls / Q000737:chemistry; D018922:HL-60 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000633:toxicity; D007211:Indoles / Q000138:chemical synthesis* / Q000633:toxicity; D010755:Organophosphates / Q000737:chemistry; D010091:Oximes / Q000138:chemical synthesis* / Q000633:toxicity; D013237:Stereoisomerism; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000633:toxicity*
D000970:Antineoplastic Agents; D001577:Benzophenones; D001632:Bibenzyls; D006835:Hydrazones; D007211:Indoles; D010755:Organophosphates; D010091:Oximes; D014404:Tubulin; D050257:Tubulin Modulators; C112107:phenstatin phosphate; C040105:combretastatin