Further naphthylcombretastatins. An investigation on the role of the naphthalene moiety.
By synthesis and biological studies of new naphthalene analogues of combretastatins, we have found that the naphthalene is a good surrogate for the isovanillin moiety (3-hydroxy-4-methoxyphenyl) of combretastatin A-4, always generating highly cytotoxic analogues when combined with the 3,4,5-trimethoxyphenyl or related systems. On the other hand, when the naphthalene replaces the 3,4,5-trimethoxyphenyl moiety, the cytotoxic activity is largely decreased. The most cytotoxic naphthalene analogues of combretastatins, which also produce inhibition of tubulin polymerization, exerted their antimitotic effects through microtubule network disruption and subsequent G(2)/M arrest of the cell cycle in human cancer cells.
Maya
Ana B S
AB
Laboratorio de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
Pérez-Melero
Concepción
C
Mateo
Carmen
C
Alonso
Dulce
D
Fernández
José Luis
JL
Gajate
Consuelo
C
Mollinedo
Faustino
F
Peláez
Rafael
R
Caballero
Esther
E
Medarde
Manuel
M
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001704:Biopolymers; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D001704:Biopolymers; C496956:N,N-dimethyl-2-amino-4-(2-(3,4,5-trimethoxyphenyl)vinyl)aniline; D009281:Naphthalenes; D013267:Stilbenes; D014404:Tubulin; C058728:fosbretabulin