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 (IC
50
= 8.80 ± 0.31 μg/mL), mammary gland breast cancer (IC
50
= 7.22 ± 0.65 μg/mL) and colorectal carcinoma (IC
50
= 9.35 ± 0.61 μg/mL) cell lines.