title: One-pot synthesis of vinca alkaloids-phomopsin hybrids.
abstract: Hybrids of vinca alkaloids and phomopsin A have been elaborated with the aim of interfering with the "vinca site" and the "peptide site" of the vinca domain in tubulin. They were synthesized by an efficient one-pot procedure that directly links the octahydrophomopsin lateral chain to the velbenamine moiety of 7'-homo-anhydrovinblastine. In their modeled complexes with tubulin, these hybrids were found to superimpose nicely on the tubulin-bound structures of vinblastine and phomopsin A. This good matching can account for the fact that two of them are very potent inhibitors of microtubules assembly and are cytotoxic against four cancer cell lines.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, UPR 2301 du CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette Cedex, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Gherbovet
authors.forename: Claire
authors.initials: C
authors.lastname: Coderch
authors.forename: María Concepción
authors.initials: MC
authors.lastname: García Alvarez
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bignon
authors.forename: Sylviane
authors.initials: S
authors.lastname: Thoret
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéritte
authors.forename: Federico
authors.initials: F
authors.lastname: Gago
authors.forename: Fanny
authors.initials: F
authors.lastname: Roussi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D009183:Mycotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009842:Oligopeptides
chemical_list: D000970:Antineoplastic Agents; D009183:Mycotoxins; D014404:Tubulin; D050257:Tubulin Modulators; D014747:Vinblastine; C035753:phomopsin; D009842:Oligopeptides