Synthesis, characterization and structure optimization of a series of thiazolidinone derivatives as Entamoeba histolytica inhibitors

A series of thiazolidinone derivatives were synthesized by sodium acetate assisted cyclization of 1-isobutyl-3-phenylthiourea with chloroacetic acid followed by the piperidine facilitated substitution of the resulting thiazolidinone with different substituted aldehydes. The ethene and imine double bonds adopt (Z,Z) configuration as indicated by 1H–1H COSY and 2D-NOESY 1H NMR and further confirmed by the crystal structure studies. The in vitro antiamoebic activity of these compounds was evaluated against HM1:IMSS strain of Entamoeba histolytica. Eight compounds exhibited promising activity with IC50 values (0.11–0.172 μM) lower than the standard drug metronidazole (IC50 1.64 μM). In vitro cytotoxicity results revealed low cytotoxic up to the concentration of 25 μM.

Graphical abstractSynthesis of thiazolidinone derivatives and their antiamoebic activity; eight of them were found to be more active than the standard drug and their non-cytotoxic nature revealed up to 25 μM.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis and characterization of new thiazolidinone derivatives. ► Crystal structure study to determine geometrical isomerism. ► The in vitro antiamoebic (HM1:IMSS) activities of the synthesized derivatives. ► Cytotoxicity against HepG2 cell line. ► All the active compounds were nontoxic at the concentration range of 3.13–25 μM.