Zeolite-Catalyzed Stereoselective Synthesis of Glycosylated 4-Thiazolidinones with Selective Anticancer Activity Against Rhabdomyosarcoma

Abstract

A microwave-assisted three-component reaction was developed for the synthesis of 4-thiazolidinones bearing a glycosidic residue, focusing on the effect of solvent variation and the use of zeolites as Lewis acid catalysts. The catalytic performance of various zeolites was evaluated, revealing a significant improvement in reaction yields and notable chemo- and diastereoselectivity. Among them, ZSM-5 showed outstanding selectivity and efficiency. The study was further extended to the biological evaluation of the isolated stereoisomers as potential Akt inhibitors. Cytotoxicity assays in rhabdomyosarcoma cell lines and normal skeletal muscle cells demonstrated that a novel glycosylated 4-thiazolidinone exhibits selective anticancer activity with minimal impact on healthy cells, highlighting its potential as a targeted therapeutic agent.