Laboratório de Síntese de Substâncias de Selênio Bioativas (LabSelen), Departamento de Química, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
Laboratório de Bioquímica Experimental (LABIOEX), Departamento de Bioquímica, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil.
Eur J Med Chem. 2018 Jul 15;155:503-515. doi: 10.1016/j.ejmech.2018.06.026. Epub 2018 Jun 11.
Novel pyrimidinic selenoureas were synthesized and evaluated against tumour and normal cell lines. Among these, the compound named 3j initially showed relevant cytotoxicity and selectivity for tumour cells. Three analogues of 3j were designed and synthesized keeping in view the structural requirements of this compound. Almost all the tested compounds displayed considerable cytotoxicity. However, 8a, one of the 3j analogues, was shown to be highly selective and cytotoxic, especially for breast carcinoma cells (MCF-7) (IC = 3.9 μM). Furthermore, 8a caused DNA damage, inhibited cell proliferation, was able to arrest cell cycle in S phase, and induced cell death by apoptosis in human breast carcinoma cells. Moreover, predictions of pharmacokinetic properties showed that 8a may present good absorption and permeation characteristics for oral administration. Overall, the current study established 8a as a potential drug prototype to be employed as a DNA interactive cytotoxic agent for the treatment of breast cancer.
新型嘧啶硒脲类化合物被合成并评估对肿瘤和正常细胞系的作用。在这些化合物中，名为 3j 的化合物最初显示出对肿瘤细胞具有相关的细胞毒性和选择性。根据该化合物的结构要求，设计并合成了 3j 的三个类似物。几乎所有测试的化合物都显示出相当大的细胞毒性。然而，8a（3j 的类似物之一）被证明具有高度的选择性和细胞毒性，特别是对乳腺癌细胞（MCF-7）（IC=3.9 μM）。此外，8a 可引起 DNA 损伤，抑制细胞增殖，能够将细胞周期阻滞在 S 期，并通过细胞凋亡诱导人乳腺癌细胞死亡。此外，药代动力学性质的预测表明，8a 可能具有良好的口服吸收和渗透特性。总的来说，本研究确立了 8a 作为一种潜在的药物原型，可作为用于治疗乳腺癌的 DNA 相互作用细胞毒性剂。
