title: Conformationnally restricted naphthalene derivatives type isocombretastatin A-4 and isoerianin analogues: synthesis, cytotoxicity and antitubulin activity.
abstract: A novel series of dihydronaphtalene, tetrahydronaphtalene and naphtalene derivatives as restricted analogues of isoCA-4 were designed, synthesized and evaluated for their anticancer properties. High cell growth inhibition against four tumour cell lines was observed at a nanomolar level with dihydronaphtalenes 1d, e and 1h, tetrahydronaphtalene 2c and naphtalene 3c. Structure-activity relationships are also considered. These compounds exhibited a significant inhibitory activity toward tubulin polymerization (IC(50) = 2-3 μM), comparable to that of isoCA-4. The effect of the lead compounds 1e and 2c on the cancer cells tested was associated with cell cycle arrest in the G(2)/M phase. Docking studies reveal that these compounds showed a binding mode similar to those observed with their non-constraint isoCA-4 and isoerianin congeners.
authors.affiliation: Univ. Paris-Sud, CNRS, BioCIS-UMR 8076, LabEx LERMIT, Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Evelia
authors.initials: E
authors.lastname: Rasolofonjatovo
authors.forename: Olivier
authors.initials: O
authors.lastname: Provot
authors.forename: Abdallah
authors.initials: A
authors.lastname: Hamze
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodrigo
authors.forename: Jérome
authors.initials: J
authors.lastname: Bignon
authors.forename: Joanna
authors.initials: J
authors.lastname: Wdzieczak-Bakala
authors.forename: Déborah
authors.initials: D
authors.lastname: Desravines
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Brion
authors.forename: Mouad
authors.initials: M
authors.lastname: Alami
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001554:Benzene / Q000737:chemistry*; D001632:Bibenzyls / Q000737:chemistry*; D045744:Cell Line, Tumor; D002733:Chlorophenols / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D010456:Peptides, Cyclic / Q000737:chemistry*; D019800:Phenol; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D014404:Tubulin / Q000737:chemistry*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001632:Bibenzyls; D002733:Chlorophenols; C477638:Erianin; D009281:Naphthalenes; D010456:Peptides, Cyclic; D014404:Tubulin; D050257:Tubulin Modulators; C031721:naphthalene; D019800:Phenol; C023490:complestatin; D001554:Benzene