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

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.

A novel BH3 mimetic Bcl-2 inhibitor promotes autophagic cell death and reduces in vivo Glioblastoma tumor growth

“…There have been several studies determining the anticancer effects of 4-thiazolidinone derivatives. More commonly studied derivatives are thiazolidine and 4-thiazolidinone, and it has been shown that these molecules have anticancer effects on several cancers including chronic myeloid leukemia, lung carcinoma, breast cancer, prostate cancer, oral cancer, colorectal cancer, neuroblastoma, and glioma [ 27 – 32 ]. While thiazolidine and 4-thiazolidinone derivatives exhibit different mechanisms of action to exert their anticancer effects, only a few of many studies reported their relation with autophagy pathways [ 33 , 34 ].…”

Imidazolidinones Derivatives As Pioneering Anticancer Agents: Unraveling Insights Through synthesis And Structure‐Activity Exploration

“…This discussion will encompass the nuances of structure-activity relationships, providing a rational framework for interpreting observed biological activities. [19,20] This review seeks to provide a holistic view of the use of imidazolidinone derivatives as pioneering anticancer agents. By unraveling insights from their synthesis to structure-activity exploration, we aim to contribute valuable knowledge to the field of medicinal chemistry, guiding future research endeavors toward the development of innovative and effective anticancer therapeutics.…”

“…As we explore the in vitro anticancer activities of imidazolidinone derivatives, a comprehensive understanding of their efficacy in different cancer cell lines and animal models will be presented. This discussion will encompass the nuances of structure‐activity relationships, providing a rational framework for interpreting observed biological activities [19,20] . This review seeks to provide a holistic view of the use of imidazolidinone derivatives as pioneering anticancer agents.…”