Vale Nuno, Correia-Branco Ana, Patrício Bárbara, Duarte Diana, Martel Fátima
UCIBIO/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences of University of Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal; Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy of University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine of University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; i3S, University of Porto's Institute for Research and Innovation in Health, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
Bioorg Med Chem Lett. 2017 Aug 1;27(15):3507-3510. doi: 10.1016/j.bmcl.2017.05.073. Epub 2017 May 26.
The investment in cancer research is critical to find more and better treatments, but essentially to save lives. Here, we describe the synthesis and characterization on new bromothiazole derivatives with amino acids and with core of nitazoxanide, an FDA-approved antiprotozoal drug. Using a human adenocarcinoma-derived cell line (the Caco-2 cell line), we then investigated the antiproliferative (H-thymidine incorporation) and cytotoxic (extracellular lactate dehydrogenase activity) effect of these derivatives. All the derivatives caused a concentration-dependent decrease in cell proliferation and viability. At their highest concentration, all compounds were able to reduce H-thymidine incorporation by more than 80%, corresponding to a more marked antiproliferative effect than butyrate. As to their cytotoxic effect, it was comparable to that of butyrate. The ability of bromo substituent in thiazole ring with new sequences of amino acids in inducing cell death and apoptosis in Caco-2 cells (and other cell lines) is now being studied.
对癌症研究的投资对于找到更多更好的治疗方法至关重要，但本质上是为了挽救生命。在此，我们描述了含氨基酸且以硝唑尼特（一种美国食品药品监督管理局批准的抗原生动物药物）为核心的新型溴噻唑衍生物的合成与表征。然后，我们使用一种人源腺癌衍生细胞系（Caco-2细胞系），研究了这些衍生物的抗增殖作用（H-胸苷掺入）和细胞毒性作用（细胞外乳酸脱氢酶活性）。所有衍生物均导致细胞增殖和活力呈浓度依赖性下降。在其最高浓度下，所有化合物均能使H-胸苷掺入减少80%以上，这对应着比丁酸盐更显著的抗增殖作用。至于它们的细胞毒性作用，则与丁酸盐相当。目前正在研究噻唑环中的溴取代基与新的氨基酸序列在诱导Caco-2细胞（以及其他细胞系）死亡和凋亡方面的能力。
