Ingold Mariana, Dapueto Rosina, Victoria Sabina, Galliusi Germán, Batthyàny Carlos, Bollati-Fogolín Mariela, Tejedor David, García-Tellado Fernando, Padrón José M, Porcal Williams, López Gloria V
Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
Cell Biology Unit, Institut Pasteur Montevideo, Mataojo 2020, 11400 Montevideo, Uruguay.
Eur J Med Chem. 2018 Jan 1;143:1888-1902. doi: 10.1016/j.ejmech.2017.11.003. Epub 2017 Nov 3.
A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for biological tests. The evaluation of the antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr (colon) provided lead compounds with GI values between 1 and 5 μM. A structure-activity relationship is also discussed. One of the studied compounds comes up as a future candidate for the development of potent tocopherol-mimetic therapeutic agents for cancer.
通过Passerini和Ugi多组分反应，在水相或无溶剂条件下开发了一种一锅法高效、实用且环保的生育酚类似物合成方法。这些反应可以使用微波辐射或超声作为能源进行优化。据此，制备了一个包含30种化合物的小型文库用于生物学测试。对人实体瘤细胞系A549（肺癌）、HBL - 100（乳腺癌）、HeLa（宫颈癌）、SW1573（肺癌）、T - 47D（乳腺癌）和WiDr（结肠癌）的抗增殖活性评估提供了GI值在1至5 μM之间的先导化合物。还讨论了构效关系。所研究的化合物之一有望成为开发用于癌症的强效生育酚模拟治疗剂的未来候选物。
