Physiological Sciences Graduate Program, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Morphology Department, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
Health Science Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil; Morphology Department, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
Toxicol In Vitro. 2024 Apr;96:105786. doi: 10.1016/j.tiv.2024.105786. Epub 2024 Feb 1.
Gliomas are among the most common primary malignant brain tumors. Despite advances in cancer treatment, survival is very low, so the discovery of new therapeutic agents is essential. In this context, indole is an important source for the development of new bioactive molecules. A pharmacological screening of ten indole derivatives was carried out to evaluate the cytotoxic capacity against three tumor cell lines. After pharmacological screening, three compounds were selected, based on their high capacity to reduce cell proliferation, and their IC values were determined. Compound 9 exhibited the highest cytotoxic activity (IC = 0.4 μg/mL) in gliomas (C6 cell line), and were selected for further experiments. C6 cells were treated with compound 9 to evaluate cellular mechanisms such as colony formation and cell migration capacity and morphological alterations. Compound 9 decreased clone formation (0.4 and 0.8 μg/mL), and inhibited migration (0.2-0.8 μg/mL) in C6 cells. Morphological changes in cells treated with the compound 9 were also observed, such as chromatin condensation, and disorganization in cellular stress beams. Indole derivatives had a cytotoxic effect on tumor cells, and compound 9 showed the best anti-proliferative and anti-migratory activity in glioma cells.
神经胶质瘤是最常见的原发性恶性脑肿瘤之一。尽管癌症治疗取得了进展,但存活率非常低,因此发现新的治疗剂至关重要。在这种情况下,吲哚是开发新的生物活性分子的重要来源。对十种吲哚衍生物进行了药理学筛选,以评估它们对三种肿瘤细胞系的细胞毒性。经过药理学筛选,根据其高增殖抑制能力选择了三种化合物,并确定了它们的 IC 值。化合物 9 在神经胶质瘤(C6 细胞系)中表现出最高的细胞毒性活性(IC = 0.4 μg/mL),并被选为进一步的实验。用化合物 9 处理 C6 细胞,以评估细胞克隆形成和细胞迁移能力以及形态改变等细胞机制。化合物 9 降低了 C6 细胞的克隆形成(0.4 和 0.8 μg/mL)和迁移(0.2-0.8 μg/mL)。还观察到用该化合物处理的细胞发生形态变化,如染色质浓缩和细胞应激梁的紊乱。吲哚衍生物对肿瘤细胞具有细胞毒性作用,化合物 9 在神经胶质瘤细胞中表现出最好的抗增殖和抗迁移活性。