1434871-06-3Relevant academic research and scientific papers
On the synthesis and biological properties of isocombretastatins: A case of ketone homologation during Wittig reaction attempts
Stocker, Vivien,Ghinet, Alina,Leman, Marie,Rigo, Benoit,Millet, Regis,Farce, Amaury,Desravines, Deborah,Dubois, Joelle,Waterlot, Christophe,Gautret, Philippe
, p. 3683 - 3696 (2013/04/11)
New isocombretastatins were synthesized by reacting the corresponding phenstatin analogs with CH3PPh3Br in presence of tBuOK. These new derivatives showed significant activities against cellular proliferation and tubulin polymerization. In particular, monomethoxylated derivatives of phenstatin and isoCA-4 exhibit similar activities to those of parent phenstatin. Attempts of the Wittig reaction on 2- (or 4-) methoxy-4′-nitrobenzophenones in the same conditions do not lead to the expected isocombretastatins but to methyleneketones with the exclusion of triphenylphosphine. A mechanism for this new ketone homologation was proposed.
Synthesis and biological evaluation of fluoro analogues of antimitotic phenstatin
Ghinet, Alina,Tourteau, Aurélien,Rigo, Beno?t,Stocker, Vivien,Leman, Marie,Farce, Amaury,Dubois, Jo?lle,Gautret, Philippe
, p. 2932 - 2940 (2013/07/05)
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).
