LabSelen-NanoBio - Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Laboratório de Biotecnologia do Câncer, Programa de Pós-Graduação em Biotecnologia (PPGB), Centro de Desenvolvimento Tecnológico (CDTec), Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS Cep 96010-900, Brazil.
Bioorg Med Chem. 2020 May 1;28(9):115423. doi: 10.1016/j.bmc.2020.115423. Epub 2020 Mar 16.
Approximately 90% of bladder carcinomas are of the urothelial carcinoma type, which are characterized by high rates of recurrence and predisposition to progress to invasive tumors, representing one of the most costly neoplasms for health systems. Intravesical chemotherapy is a standard for the treatment of non-invasive bladder cancer. However, chemotherapy is usually aggressive and cytotoxic, which increases the death rates caused by cancer. Heterocyclic compounds which exhibit favorable pharmacokinetic and pharmacodynamic properties may enhance drug affinity for a target protein by targeting the treatment. Thus, this work presents the synthesis, characterization, and in vitro biological evaluation of new antioxidant (inhibition of lipid peroxidation, scavenging of free radical DPPH, and thiol peroxidase-like activity) and antiproliferative chalcogenobiotin derivatives and tests them against bladder carcinoma 5637 cells. A prominent response was obtained for the selected compounds, with tellurium biotin derivatives displaying effective antioxidant and antiproliferative activity. The effective compounds also demonstrated no toxicity in in vitro or in vivo studies.
大约 90%的膀胱癌为尿路上皮癌,其特点是复发率高,易进展为侵袭性肿瘤,是对卫生系统造成最大花费的肿瘤之一。膀胱内化疗是治疗非浸润性膀胱癌的标准方法。然而,化疗通常具有侵袭性和细胞毒性,这会增加癌症导致的死亡率。具有良好药代动力学和药效学特性的杂环化合物可以通过靶向治疗来增强药物对靶蛋白的亲和力。因此,这项工作提出了新的抗氧化剂(抑制脂质过氧化、清除自由基 DPPH 和硫氧还蛋白样活性)和抗增殖硒代生物素衍生物的合成、表征和体外生物学评价,并对膀胱癌 5637 细胞进行了测试。选定的化合物表现出明显的反应,碲代生物素衍生物表现出有效的抗氧化和抗增殖活性。有效化合物在体外或体内研究中也没有显示出毒性。