Department of Organic Chemistry, Al. I. Cuza University of Iasi, Faculty of Chemistry, Bd., Carol I, nr. 11, 700506 Iasi, Romania.
Bioorg Med Chem. 2013 Jun 1;21(11):2932-40. doi: 10.1016/j.bmc.2013.03.064. Epub 2013 Apr 4.
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).
目的在于研究氟的影响，特别是对 A 环的影响，我们合成了一系列新的苯并菲斯汀（phenstatin）的氟代类似物（7a-l），并测试了它们与微管蛋白聚合的相互作用，同时还评估了它们对 NCI-60 人类癌细胞系的细胞毒性。我们已经表明，用 2,4,5-三氟-3-甲氧基苯基单元取代苯并菲斯汀的 3,4,5-三甲氧基苯基 A 环，既保留了抗微管蛋白作用，又保留了细胞毒性。氟代异康布他汀 7k 是本研究中最有效的抗癌药物，对白血病细胞系 SR（GI50=15 nM）和 HL-60（TB）（GI50=23 nM）以及黑色素瘤细胞系 MDA-MB-435（GI50=19 nM）表现出最高的增殖抑制潜力。
