With the aim of discovering new anticancer agents, we have designed and synthesized novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases. The synthesis started with the selective nitration at 5-position of 6-hydroxybenzo[d][1,3]oxathiol-2-one (1) leading to the nitro derivative 2. The nitro group of 2 was reduced to give the amino intermediate 3. Schiff bases 4a–r were obtained from coupling reactions between 3 and various benzaldehydes and heteroaromatic aldehydes. All the new compounds were fully identified and characterized by NMR (¹H and ¹³C) and specifically for 4q by X-ray crystallography. The in vitro cytotoxicity of the compounds was evaluated against cancer cell lines (ACP-03, SKMEL-19 and HCT-116) by using MTT assay. Schiff bases 4b and 4o exhibited promising cytotoxicity against ACP-03 and SKMEL-19, respectively, with IC₅₀ values lower than 5 μM. This class of compounds can be considered as a good starting point for the development of new lead molecules in the fight against cancer.

Mercaptoacetic acid (3), also known as thioglycolic acid, is a liquid miscible with water and with most organic solvents such as alcohols, ether, chloroform and benzene.[ ¹ ] It is widely described in the literature, especially as a substrate for the synthesis of pharmacologically active heterocycles[ ² ] including 1,3-thiazolidin-4-ones,[ ³ ] 1,4-thiazepines[ ⁴ ] and thiazoles.[ ⁵ ] It is also used for the formation of spiro derivatives,[ ⁶ ] in multicomponent reactions, and in removing the nosyl protecting group from amine functions of α-amino acids.[ ⁷ ]