Departament de Ciències Fisiològiques II, University of Barcelona, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat (Spain).
Angew Chem Int Ed Engl. 2014 Sep 15;53(38):10150-4. doi: 10.1002/anie.201405758. Epub 2014 Sep 5.
A new class of small molecules, with an unprecedented trifluorothiazoline scaffold, were synthesized and their pro-apoptotic activity was evaluated. With an EC50 in the low micromolar range, these compounds proved to be potent inducers of apoptosis in a broad spectrum of tumor cell lines, regardless of the functional status of p53. Fast structure-activity relationship studies allowed the preparation of the strongest apoptosis-inducing candidate. Using a high performance affinity purification approach, we identified prohibitins 1 and 2, key proteins involved in the maintenance of cell viability, as the targets for these compounds.
我们合成了一类新型小分子，具有前所未有的三氟噻唑啉骨架，并评估了它们的促凋亡活性。这些化合物在低微摩尔浓度范围内具有活性，能够在广泛的肿瘤细胞系中诱导凋亡，而与 p53 的功能状态无关。快速的构效关系研究允许制备最强的诱导凋亡候选物。使用高效亲和力纯化方法，我们确定了参与细胞存活维持的关键蛋白——抑素 1 和 2，为这些化合物的靶标。
