Synthesis and antiproliferative activity of new thiazole hybrids with [3.3.0]furofuranone or tetrahydrofuran scaffolds Scientific paper

Abstract

New thiazole hybrids were synthesized and evaluated for their in vitro cytotoxicity against a panel of human malignant cell lines. The key steps in the synthesis of hybrids 3–7 involved the initial condensation of appropriate aldo­nonitriles with cysteine ethyl ester hydrochloride, followed by subsequent treatment of resulting thiazolines with diazabicycloundecene to form the thiaz­ole ring. Bioiso­steres 8 and 14 have been prepared after the stereoselective addition of 2-(tri­methylsilyl)thiazole to the hemiacetals obtained by periodate cleavage of terminal diol functionality in the suitably protected d-glucose der­ivatives. The obtained analogues showed various antiproliferative activities in the cultures of several tumour cell lines. Hybrid 6 was the most potent in HeLa cells, exhibiting more than 10 and 4 times stronger activity than both leads 1 and 2, respectively. The most active compound in Raji cells was hybrid 12, which was nearly 2-fold more potent than the clinical antitumour drug doxo­rubicin. All analogues were more potent in A549 cells with respect to lead 1, while compounds 6 and 7 were slightly more active than doxorubicin. Prelim­inary structure–activity relationship analysis revealed that the presence of a cinnamate group at the C-3 pos­ition in analogues of type 7 increases the act­ivity of resulting molecular hybrids.