Synthesis and cytotoxic evaluation of mesna adducts of some 1-aryl-4,4-dimethyl-5-(1-piperidino)-1-penten-3-one hydrochlorides

Abstract

Reaction of 1-(4-bromophenyl)-4,4-dimethyl-5-(1-piperidino)-1-penten-3-one hydrochloride (1f) with sodium 2-mercaptoethanesulphonate (mesna) gave rise to the thiol adduct. 3. Recrystallization of this compound led to the formation of the corresponding zwitterion 4f. A series of analogues of 4f were prepared and the structure of a representative compound was confirmed by X-ray crystallography. In general, the thiol adducts had similar activity towards P388 cells and human tumour cell lines as the precursor enones 1 although greater selectivity to malignant diseases was found with the thiol adducts. A stability study of representative compounds conducted by 1H NMR spectroscopy revealed that the thiol adducts decomposed in solution. In one case regeneration of the ketone was noted while for the other compounds, the decomposition products were not identified.