Synthesis and cytotoxic evaluation of combretafurans, potential scaffolds for dual-action antitumoral agents.
We have synthesized rigid analogues of combretastatin bearing a furan ring in place of the olefinic bridge. These compounds are cytotoxic at nanomolar concentrations in neuroblastoma cells, display a similar structure-activity relationship compared to combretastatin A4, and inhibit tubulin polymerization. We also show that the furan ring can be further functionalized. Thus, it is possible that combretafurans could act as scaffolds for the development of dual-action antitumoral agents.
Pirali
Tracey
T
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche and Drug and Food Biotechnology Center, Università degli Studi del Piemonte Orientale A. Avogadro, Via Bovio 6, 28100 Novara, Italy.
Busacca
Sara
S
Beltrami
Lorena
L
Imovilli
Daniela
D
Pagliai
Francesca
F
Miglio
Gianluca
G
Massarotti
Alberto
A
Verotta
Luisella
L
Tron
Gian Cesare
GC
Sorba
Giovanni
G
Genazzani
Armando A
AA
D000840:Anisoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001632:Bibenzyls / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D009447:Neuroblastoma / Q000188:drug therapy*; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects
D000840:Anisoles; D000970:Antineoplastic Agents; D001632:Bibenzyls; D005663:Furans; D013267:Stilbenes; D014404:Tubulin; C040105:combretastatin; C058728:fosbretabulin; C039281:furan