title: Further naphthylcombretastatins. An investigation on the role of the naphthalene moiety.
abstract: 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.
authors.affiliation: Laboratorio de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
authors.forename: Ana B S
authors.initials: AB
authors.lastname: Maya
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez-Melero
authors.forename: Carmen
authors.initials: C
authors.lastname: Mateo
authors.forename: Dulce
authors.initials: D
authors.lastname: Alonso
authors.forename: José Luis
authors.initials: JL
authors.lastname: Fernández
authors.forename: Consuelo
authors.initials: C
authors.lastname: Gajate
authors.forename: Faustino
authors.initials: F
authors.lastname: Mollinedo
authors.forename: Rafael
authors.initials: R
authors.lastname: Peláez
authors.forename: Esther
authors.initials: E
authors.lastname: Caballero
authors.forename: Manuel
authors.initials: M
authors.lastname: Medarde
mesh_terms: 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
chemical_list: 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