Ghinet Alina, Moise Iuliana-Monica, Rigo Benoît, Homerin Germain, Farce Amaury, Dubois Joëlle, Bîcu Elena
Department of Organic Chemistry, 'Al. I. Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania; Inserm U995, LIRIC, Université de Lille, CHRU de Lille, Faculté de médecine-Pôle recherche, Place Verdun, F-59045 Lille Cedex, France; Hautes Etudes d'Ingénieur (HEI), Groupe HEI-ISA-ISEN, UCLille, Laboratoire de Pharmacochimie, 13 rue de Toul, F-59046 Lille, France.
Department of Organic Chemistry, 'Al. I. Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania.
Bioorg Med Chem. 2016 May 15;24(10):2307-17. doi: 10.1016/j.bmc.2016.04.001. Epub 2016 Apr 1.
New phenothiazine derivatives 6-20 have been designed, synthesized and evaluated in vitro for their ability to inhibit tubulin polymerization and antiproliferative activity against 60 cancer cell lines, including several multi-drug resistant (MDR) tumor cell lines. The phenothiazine unit may successfully replace the classical 3,4,5-trimethoxyphenyle A ring of parent combretastatin A-4 or phenstatin, confirming previous studies. The most promising structural modulations have been realized on the B ring, the 2'-fluoro-4'-methoxy substitution in compound 6 and the 2'-trifluoromethyl-4'-methoxy substitution in compound 7 providing the best antitubulin and antitumor activity in the current study. Compounds 6-8 and 16 exhibited more important cell growth inhibition than parent phenstatin 2 on human colon Duke's type D, colorectal adenocarcinoma COLO 205 and on human kidney adenocarcinoma A498 cell lines. 10-Methylphenothiazine derivatives 19 and 20 did not show biological activity but exerted bright fluorescence and solvatochromism effects. These molecules deserve further chemical efforts in order to provide valuable tools for biophysical studies.
新型吩噻嗪衍生物6 - 20已被设计、合成并在体外评估其抑制微管蛋白聚合的能力以及对60种癌细胞系（包括几种多药耐药（MDR）肿瘤细胞系）的抗增殖活性。吩噻嗪单元可能成功取代了母体康普他汀A - 4或苯他汀经典的3,4,5 - 三甲氧基苯基A环，证实了先前的研究。最有前景的结构修饰是在B环上实现的，化合物6中的2'-氟-4'-甲氧基取代和化合物7中的2'-三氟甲基-4'-甲氧基取代在当前研究中提供了最佳的抗微管蛋白和抗肿瘤活性。化合物6 - 8和16对人结肠癌杜克D型、结肠腺癌COLO 205和人肾腺癌A498细胞系表现出比母体苯他汀2更显著的细胞生长抑制作用。10 - 甲基吩噻嗪衍生物19和20没有显示出生物活性，但具有明亮的荧光和溶剂化显色效应。这些分子值得进一步的化学研究，以便为生物物理研究提供有价值的工具。
