Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety

Abstract

Antitumor screening of several novel 4-thiazolidinones with benzothiazole moiety has been performed. Reactions of (benzothiazole-2-yl)hydrazine with trithiocarbonyl diglycolic acid or 6-methyl-2-aminobenzothiazole with 2-carbethoxymethylthio-2-thiazoline-4-one have yielded starting 3- (1) or 2-substituted (11) 4-thiazolidinones which have been subsequently utilized in a Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 2-10, 12-16. Compound 11 has been obtained alternatively by a counter synthesis method based on the reaction of 2-chloro-N-(6-methylbenzothiazol-2-yl)-acetamide and ammonium thiocyanate. The structures of compounds have been determined by (1)H, (13)C NMR, IR and X-ray analysis. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute and two (6, 16) of them has revealed the anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancers cell lines. Among tested compounds, 2-{2-[3-(benzothiazol-2-ylamino)-4-oxo-2-thioxothiazolidin-5-ylidenemethyl]-4-chlorophenoxy}-N-(4-methoxyphenyl)-acetamide (6) was found to be the most active candidate with average logGI(50) and logTGI values -5.38 and -4.45 respectively.