The synthesis, structure elucidation and studies of biological activities of new substituted thioureas and their cyclization derivatives

This research is composed of two parts. In the first part; a novel series of thiourea derivatives [1-17] were synthesized by the reaction of 4-(4-flourophenoxy)aniline and the different isothiocyanates. In the second part; 2-imino-1,3-thiazolidine-4-one and 2-imino-1,3-thiazolidine-4,5-dione derivatives were obtained by oxidative cyclization of thioureas. Thiourea derivatives [1-17] were reacted with oxalyl chloride in presence of diclorometane to form 2-imino-1,3-thiazolidine-4,5-dione derivatives [1a-17a]. Other compounds that 2-imino-1,3-thiazolidine-4-one derivatives [1b-17b] were synthesized by condensation of thiourea derivatives [1-17] and ethyl bromoacetate in the presence of triethylamine and ethanol. The purity of compounds were controlled by TLC and the chemical structures of the synthesized compounds were elucidated using UV, IR, 1H NMR, 13C NMR, 19F NMR, mass spectroscopy and elemental analysis. The biological activities of synthesized thiourea derivatives have been screened as antioxidant, acetylcholinesterase (AChE), butyrycholinesterase (BChE) and anticancer activity. Among the thiourea derivatives, compound 13 (IC50 2,45±0,12 µM) inhibited AChE better than galantamine (IC50 4,48±0,78 µM) and compound 17 (IC50 5,11±0,15 µM) had the best activity in BChE assay. All the synthesized thiourea derivatives were evaluated for their in vitro cancer activity against the human breast cancer cell lines MCF-7 (human breast adenocarcinoma) and SKBr-3 (human epithelial breast adenocarcinoma). Most of the derivatives exhibited significant anticancer activity. Especially, compound 3 showed the most potent activity (IC50 20.1µM) against SKBr-3 when compared with the drugs 5-fluorouracil and cisplatin and most importantly, it did not affect normal breast epithelial cells (4010).