Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Novo Edifício do Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal.
Molecules. 2021 May 31;26(11):3315. doi: 10.3390/molecules26113315.
Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline-chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI values below 10 µM for the three tested cell lines, and structure-activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.
硫代黄酮是天然黄酮的生物等排体。它们具有多种活性，包括抗肿瘤活性。因此，我们合成了一系列硫代黄酮，但出乎意料的是，我们得到了四个具有喹唑啉-色烯骨架的四环硫代黄酮。我们研究了这些化合物对 A375-C5、MCF-7 和 NCI-H460 三种肿瘤细胞的生长抑制活性。我们还进行了光物理研究。其中两种化合物对三种测试细胞系的 GI 值低于 10µM，我们建立了构效关系研究。三种化合物的吸收和发射波长相似，这是具有推拉特性的染料的特征。通过 X 射线晶体学解析了两种化合物的结构。两种四环硫代黄酮化合物成为了命中化合物。其中一种化合物在细胞内积累，作为绿色荧光染料，通过荧光显微镜和流式细胞术进行分析，使其成为一种很有前途的治疗癌症的候选药物。
