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.