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2,4-Thiazolidinedione as Precursor to the Synthesis of Compounds with Antiglioma Activities in C6 and GL261 Cells

Author(s):

Alana de Vasconcelos, Ana Júlia Zulian Boeira, Bruna Bento Drawanz, Nathalia Stark Pedra, Natália Pontes Bona, Francieli Moro Stefanello and Wilson Cunico*   Pages 1 - 10 ( 10 )

Abstract:


Objective: This study aims to synthesize and characterize 2,4-thiazolidinediones and evaluate their antitumor activity.

Method: 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 thin-layer chromatography (TLC). Compounds were identified and characterized using gas chromatography coupled to mass spectrometry (CG-MS) and hydrogen (1 H-NMR) and carbon nuclear magnetic resonance spectroscopy (13C-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 IC50.

Results: 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: IC50 of 28.51 μM and 54.26 μM, respectively.

Conclusion: The compounds were not cytotoxic in astrocyte culture, demonstrating selectivity for malignant cells. Changes in both rings are important for antiglioma activity in the cell lines tested. TZD 4CI had the best antiglioma activity.

Keywords:

Thiazolidinedione, antiglioma, astrocyte, one-pot reaction, Knoevenagel, microwave synthesis.

Affiliation:

Laboratório de Química Aplicada à Bioativos (LaQuiABio), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, Laboratório de Química Aplicada à Bioativos (LaQuiABio), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, Laboratório de Química Aplicada à Bioativos (LaQuiABio), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, Laboratório de Neuroquímica, inflamação e Câncer (Neurocan) Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, Laboratório de Neuroquímica, inflamação e Câncer (Neurocan) Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, Laboratório de Neuroquímica, inflamação e Câncer (Neurocan) Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, Laboratório de Química Aplicada à Bioativos (LaQuiABio), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS



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