CNRS UMR8151, INSERM U1022, Unité de Pharmacologie Chimique, Génétique & Imagerie, Ecole Nationale Supérieure de Chimie de Paris (Chimie ParisTech), PSL,11 rue Pierre & Marie Curie, Paris 75005, France.
Eur J Med Chem. 2013 Feb;60:360-4. doi: 10.1016/j.ejmech.2012.12.025. Epub 2012 Dec 20.
In order to find new molecules with cytotoxic activity against cancer cells, we prepared bis-akyne amides derived from propiolic acid. The bis-alkynes were then transformed in their mono-1,2,3-triazole analogs onto the amide side, due to its greater reactivity, using a catalyst-free Huisgen's reaction. The mono-triazoles were then subjected to the copper (I)-catalyzed version of the previous reaction (CuAAC), using a supported catalyst, to produce bis-triazoles. All products were obtained pure after simple trituration or filtration procedures. All synthetic compounds were tested in vitro for their cytotoxic activity using B16 melanoma cells. Four compounds (7, 23, 25 and 33) showed activities in the micromolar range (<21 μM) whereas three compounds (3, 22 and 38) presented activity at low micromolar concentrations (<10 μM), and two analogs (2 and 13) were active at nanomolar levels (<1 μM).
为了寻找具有细胞毒性的抗癌新分子，我们制备了源自丙炔酸的双炔酰胺。由于其更高的反应性，我们使用无催化剂的 Huisgen 反应将双炔转化为其单 1,2,3-三唑类似物。然后，我们使用负载型催化剂将单三唑进行铜（I）催化的前一步反应（CuAAC），以生成双三唑。所有产物在经过简单的研磨或过滤后均得到纯品。我们使用 B16 黑色素瘤细胞在体外测试了所有合成化合物的细胞毒性活性。四种化合物（7、23、25 和 33）在微摩尔范围内（<21 μM）表现出活性，而三种化合物（3、22 和 38）在低微摩尔浓度下（<10 μM）表现出活性，两种类似物（2 和 13）在纳摩尔水平（<1 μM）下具有活性。
