title: Synthesis and cytotoxic evaluation of combretafurazans.
abstract: Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins embodying a furazan ring (combretafurazans). To achieve this, we have developed a new strategy that exploits the dehydration of vicinal dioximes using the Mitsunobu reaction. Among the advantages of following such a strategy are the mild conditions used for the construction of the diarylfurazan derivatives, allowing for the presence of highly functionalized substrates and deactivated aromatic rings. Combretafurazans are more potent in vitro cytotoxic compounds compared to combretastatins in neuroblastoma cells, yet maintaining similar structure-activity relationship and pharmacodynamic profiles.
authors.affiliation: Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Universitá del Piemonte Orientale "A. Avogadro", Via Bovio 6, 28100 Novara, Italy.
authors.forename: Gian Cesare
authors.initials: GC
authors.lastname: Tron
authors.forename: Francesca
authors.initials: F
authors.lastname: Pagliai
authors.forename: Erika
authors.initials: E
authors.lastname: Del Grosso
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorba
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001704:Biopolymers; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D008968:Molecular Conformation; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D001704:Biopolymers; D010069:Oxadiazoles; D014404:Tubulin