Laboratorio de Quimica Aplicada a Bioativos (LaQuiABio), Centro de Ciencias Quimicas, Farmaceuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitario s/n, Capao do Leao, RS, CEP: 96010-900, Brazil.
Laboratorio de Neuroquimica, inflamacao e Cancer (Neurocan) Centro de Ciencias Quimicas, Farmaceuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitario s/n, Capao do Leao, RS, CEP: 96010-900, Brazil.
Med Chem. 2021;17(6):601-610. doi: 10.2174/1573406416666200403075826.
Thiazolidinediones (TZDs) represent an important class of heterocyclic compounds that have versatile biological activities, including anticancer activity. Glioma is one of the most common primary brain tumors, and it is responsible for most of the deaths caused by primary brain tumors. In the present work, 2,4-thiazolidinediones were synthesized via a multicomponent microwave one-pot procedure. The cytotoxicity of compounds was analyzed in vitro using rat (C6) and mouse (GL261) glioblastoma cell lines and primary cultures of astrocytes.
This study aims to synthesize and characterize 2,4-thiazolidinediones and evaluate their antitumor activity.
TZDs were synthesized from three components: 2,4-thiazolidinedione, arene-aldehydes, and aryl chlorides. The reactions were carried out inside a microwave and monitored using thinlayer chromatography (TLC). Compounds were identified and characterized using gas chromatography coupled to mass spectrometry (CG-MS) and hydrogen (H-NMR) and carbon nuclear magnetic resonance spectroscopy (C-NMR). The antitumor activity was analyzed using the 3-(4,5- dimethyl)-2,5-diphenyltetrazolium bromide (MTT) reduction test, in which cell viability was verified in the primary cultures of astrocytes and in rat and mouse glioblastoma cells exposed to the synthesized compounds. The cytotoxicity of all derivatives was analyzed at the 100 μM concentration, both in astrocytes and in the mouse and rat glioblastoma cell lines. The compounds that showed the best results, 4CI and 4DI, were also tested at concentrations 25, 50, 100, 175, and 250 μM to obtain the IC.
Seventeen TZD derivatives were easily obtained through one-pot reactions in 40 minutes with yields ranging from 12% to 49%. All compounds were cytotoxic to both glioblastoma cell lines without being toxic to the astrocyte primary cell line at 100 μM, thus demonstrating a selective activity. Compounds 4CI and 4DI showed the best results in the C6 cells: IC of 28.51 μM and 54.26 μM, respectively.
The compounds were not cytotoxic in astrocyte culture, demonstrating selectivity for malignant cells. Changes in both rings are important for anti-glioma activity in the cell lines tested. TZD 4CI had the best anti-glioma activity.
噻唑烷二酮（TZDs）是一类具有多种生物活性的杂环化合物，包括抗癌活性。神经胶质瘤是最常见的原发性脑肿瘤之一，也是原发性脑肿瘤死亡的主要原因。在本工作中，通过多组分微波一锅法合成了 2,4-噻唑烷二酮。使用大鼠（C6）和小鼠（GL261）神经胶质瘤细胞系和星形胶质细胞原代培养物在体外分析了化合物的细胞毒性。
本研究旨在合成和表征 2,4-噻唑烷二酮并评估其抗肿瘤活性。
TZDs 由三个成分：2,4-噻唑烷二酮、芳烃-醛和芳基氯合成。反应在微波内部进行，并使用薄层色谱法（TLC）进行监测。使用气相色谱-质谱联用（GC-MS）和氢（H-NMR）和碳核磁共振波谱（C-NMR）对化合物进行鉴定和表征。使用 3-（4,5-二甲基）-2,5-二苯基四唑溴化物（MTT）还原试验分析抗肿瘤活性，其中通过暴露于合成化合物的星形胶质细胞原代培养物以及大鼠和小鼠神经胶质瘤细胞中验证细胞活力。在 100 μM 浓度下分析了所有衍生物的细胞毒性，无论是在星形胶质细胞还是在小鼠和大鼠神经胶质瘤细胞系中。在浓度为 25、50、100、175 和 250 μM 时，还测试了显示最佳结果的化合物 4CI 和 4DI，以获得 IC。
通过一锅反应在 40 分钟内轻松获得 17 种 TZD 衍生物，产率为 12%-49%。所有化合物在 100 μM 时对两种神经胶质瘤细胞系均具有细胞毒性，而对星形胶质细胞原代细胞系没有毒性，因此表现出选择性活性。化合物 4CI 和 4DI 在 C6 细胞中表现出最佳结果：IC 分别为 28.51 μM 和 54.26 μM。
在星形胶质细胞培养物中，化合物没有细胞毒性，对恶性细胞具有选择性。在测试的细胞系中，两个环的变化对抗神经胶质瘤活性很重要。TZD 4CI 具有最佳的抗神经胶质瘤活性。
