Synthesis and Anticancer Evaluation of New Thiazole and Thiadiazole Derivatives Bearing Acetanilide Moiety.

Abstract

New thiazole and thiadiazole derivatives bound to the acetanilide moiety were synthesized and evaluated for their cytotoxic activity. The precursor N-(4-acetamidophenyl)-N'-phenylthiourea (2) was cyclocondensed with ethyl bromoacetate to afford a mixture of the two isomers, 2-(4-acetamidophenylimino)-3-phenylthiazolidin-4-one (3a, 23%) and 3-(4-acetamidophenyl)-2-phenyliminothiazolidin-4-one (3b, 71%). The Knoevenagel reaction of 3b with various aromatic aldehydes afforded 5-arylidene-2-phenyliminothiazolidin-4-one derivatives 5a-5e. Intramolecular cyclization of thiourea scaffold 2 with chloroacetone and/or phenacyl chloride gave the conforming thiazole derivatives 6a and 6b. A new series of thiadiazole derivatives 9a-9c and 11a-11c was synthesized by the reaction of N-(4-acetamidophenyl)-N'-phenylthiourea (2) with selected derivatives of hydrazonoyl halide in ethanol and triethylamine. The structures of the synthesized thiazole and thiadiazole compounds were elucidated by their compatible spectral data. The cytotoxic activity of the synthesized thiazole and thiadiazole derivatives was screened against four human cancer cell lines and showed promising results. Thiazolidin-4-one compound 5d showed the strongest cytotoxic effects on hepatocellular carcinoma (IC50 = 8.80 ± 0.31 μg/mL), mammary gland breast cancer (IC50 = 7.22 ± 0.65 μg/mL) and colorectal carcinoma (IC50 = 9.35 ± 0.61 μg/mL) cell lines.