title: Oxaphosphinanes: new therapeutic perspectives for glioblastoma.
abstract: This paper reports the design and the synthesis of a new family of compounds, the phostines, belonging to the [1,2]oxaphosphinane family. Twenty-six compounds have been screened for their antiproliferative activity against a large panel of NCI cancer cell lines. Because of its easy synthesis and low EC(50) value (500 nM against the C6 rat glioma cell line), compound 3.1a was selected for further biological study. Moreover, the specific biological effect of 3.1a on the glioblastoma phylogenetic cluster from the NCI is dependent on its stereochemistry. Within that cluster, 3.1a has a higher antiproliferative activity than Temozolomide and is more potent than paclitaxel for the SF295 and SNB75 cell lines. In constrast with paclitaxel and vincristine, 3.1a is devoid of astrocyte toxicity. The original activity spectrum of 3.1a on the NCI cancer cell line panel allows the development of this family for use in association with existing drugs, opening new therapeutic perspectives.
authors.affiliation: INSERM U-1051, Institut des Neurosciences de Montpellier, 80 rue Augustin Fliche 34091 Montpellier, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Clarion
authors.forename: Carine
authors.initials: C
authors.lastname: Jacquard
authors.forename: Odile
authors.initials: O
authors.lastname: Sainte-Catherine
authors.forename: Séverine
authors.initials: S
authors.lastname: Loiseau
authors.forename: Damien
authors.initials: D
authors.lastname: Filippini
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Hirlemann
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Volle
authors.forename: David
authors.initials: D
authors.lastname: Virieux
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pirat
authors.forename: Norbert
authors.initials: N
authors.lastname: Bakalara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003498:Cyclic P-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010757:Phosphorous Acids; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C573291:3-hydroxy-4,5-bis(benzyloxy)-6-benzyloxymethyl-2-phenyl-2-oxo-2lambda(5)-(1,2)oxaphosphinane; D000970:Antineoplastic Agents; D003498:Cyclic P-Oxides; D063065:Organophosphonates; D010757:Phosphorous Acids