Synthesis and biological evaluation of fluoro analogues of antimitotic phenstatin |
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| Authors: | Alina Ghinet Aurélien Tourteau Benoît Rigo Vivien Stocker Marie Leman Amaury Farce Joëlle Dubois Philippe Gautret |
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| Institution: | 1. Department of Organic Chemistry, ‘Al. I. Cuza’ University of Iasi, Faculty of Chemistry, Bd., Carol I, nr. 11, 700506 Iasi, Romania;2. Univ Lille Nord de France, F-59000 Lille, France;3. UCLille, EA GRIIOT (4481), Laboratoire de Pharmacochimie, HEI, 13 Rue de Toul, F-59046 Lille, France;4. Institut de Chimie Pharmaceutique Albert Lespagnol, EA GRIIOT (4481), IFR114, 3 Rue du Pr Laguesse, B.P. 83, F-59006 Lille, France;5. Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherches de Gif, Avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France |
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| 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). |
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| Keywords: | Phenstatin Tubulin Antimitotic agent Fluorobenzophenone Eaton’s reagent |
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