title: Synthesis and evaluation of hybrid molecules targeting the vinca domain of tubulin.
abstract: Some hybrids of vinca alkaloids and phomopsin A, linked by a glycine pattern, have been synthesized in one or two steps, by an insertion reaction and shown to inhibit microtubule assembly. These compounds have been elaborated in order to interact with both the "vinca site" and the "peptide site" of the vinca domain in tubulin. Two out of three hybrids are potent inhibitors of microtubules assembly and they present good cytotoxicity against different cell lines. Molecular modelling studies show that they could bind, within the vinca domain, in similar spatial regions as those of vinca and phomopsin thanks to the flexibility provided by the glycine linker used to elaborate these hybrids.
authors: 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. fanny.roussi@cnrs.fr.
authors: O
authors: O
authors: Gherbovet
authors: Pedro A
authors: PA
authors: Sánchez-Murcia
authors: M C
authors: MC
authors: García Alvarez
authors: J
authors: J
authors: Bignon
authors: S
authors: S
authors: Thoret
authors: F
authors: F
authors: Gago
authors: F
authors: F
authors: Roussi
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D017209:Apoptosis; D001665:Binding Sites; D002460:Cell Line; D005998:Glycine / Q000737:chemistry*; D006160:Guanosine Triphosphate / Q000737:chemistry; D006801:Humans; D020014:K562 Cells; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D009183:Mycotoxins / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014404:Tubulin / Q000737:chemistry*; D014747:Vinblastine / Q000031:analogs & derivatives / Q000737:chemistry; D014748:Vinca Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000077235:Vinorelbine; D009842:Oligopeptides
chemical_list: D000470:Alkaloids; D005998:Glycine; D006160:Guanosine Triphosphate; D009183:Mycotoxins; D010455:Peptides; D014404:Tubulin; D014747:Vinblastine; D014748:Vinca Alkaloids; D000077235:Vinorelbine; C035753:phomopsin; D009842:Oligopeptides