Synthesis, anti-cancer activity, gene expression and docking stimulation of 2-thioxoimidazolidin-4-one derivatives

In this elucidation, we synthesized different 2-thioxoimidazolidin-4-one derivatives through the condensation of N -methyl glycine (1) with various alkyl isothiocyanates 2 in refluxing EtOH in the presence of morpholine for 6 h to give the hydantoins derivatives 3 which is active CH2 source for reaction of different aldehyde derivatives to afford the corresponding thioxoimidazolidin-4-one derivatives 4a-f in excellent yield. The obtained thioxoimidazolidin-4-one derivatives were investigated via spectral analysis through FT-IR, H-1 NMR and mass fragmentations. Cytotoxicity activity of synthesized compounds were examined as anticancer agents against three cancer cell lines (A549, MCF7 and HepG2 ) using neutral red uptake assay. After 48 h, treatment of MCF7 cells with 2-thioxoimidazolidin-4-one derivatives 4e,a,f revealed more inhibitory influence and compound 4a showed more cytotoxic effect on A549 cells as compared to control values. Furthermore, the expression levels of IL6, ABCG2, MYC and COX2 genes were investigated using QRT-PCR method. Moreover, these results could indicate the promising effects of compound 4e on reducing drug resistance through down regulation of IL6, ABCG2, MYC and COX2 genes when treated with MCF7 cells as compared to control values. Also, these biological results were confirmed through molecular docking with different proteins with (PDBID : 2ito), ( PDBID : 4hdq) and ( PDBID : 5h38), for A549, MCF-7 and HepG2 cells and showed low energy binding and shortage bond length, while docking for genes we take the proteins such as (PDBID : 5jsn) and (PDBID : 5vzu) which confirmed the experimental results. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, we synthesized different 2-thioxoimidazolidin-4-one derivatives and investigated their cytotoxicity activity and gene expression. The results showed potential anticancer activity and a mechanism for reducing drug resistance.