title: Synthesis and biological evaluation of fluoro analogues of antimitotic phenstatin.
abstract: With the aim of investigating the influence of fluorine, in particular on the A-ring, a new series of fluoro analogues (7a-l) of phenstatin (3) was synthesized and tested for interactions with tubulin polymerization and evaluated for cytotoxicity on an NCI-60 human cancer cell lines panel. We have shown that the replacement of 3,4,5-trimethoxyphenyl A-ring of phenstatin with 2,4,5-trifluoro-3-methoxyphenyl unit, results in the conservation of both antitubulin and cytotoxic effect. Fluoro isocombretastatin 7k was the most effective anticancer agent in the present study and demonstrated the highest antiproliferative potential on leukemia cell lines SR (GI50=15 nM) and HL-60(TB) (GI50=23 nM) and on melanoma cell line MDA-MB-435 (GI50=19 nM).
authors.affiliation: Department of Organic Chemistry, Al. I. Cuza University of Iasi, Faculty of Chemistry, Bd., Carol I, nr. 11, 700506 Iasi, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Ghinet
authors.forename: Aurélien
authors.initials: A
authors.lastname: Tourteau
authors.forename: Benoît
authors.initials: B
authors.lastname: Rigo
authors.forename: Vivien
authors.initials: V
authors.lastname: Stocker
authors.forename: Marie
authors.initials: M
authors.lastname: Leman
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.forename: Philippe
authors.initials: P
authors.lastname: Gautret
mesh_terms: D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001577:Benzophenones / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D054879:Halogenation; D006801:Humans; D020128:Inhibitory Concentration 50; D008938:Mitosis / Q000187:drug effects; D010755:Organophosphates / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D001577:Benzophenones; D017611:Fluorine Compounds; D010755:Organophosphates; D011355:Prodrugs; C112107:phenstatin phosphate