Metal ion interaction with inducer of reverse transformation of cancer cells

Abstract

Gosálvez, based on theoretical hypothesis of the function of the plasma membrane, designed three heterocycles as possible inducers of reverse transformation of cancer cells to normal phenotype [1]. Two of these compounds (thiaproline, Tp, and 2-amino-1,3-thiazoline, AT) have been taken to the anticancer clinics and have shown, preliminary, an antitumor activity [2]. Both ligands are believed to blind in the lipid environment a zinc ion linked to protein complex of the membrane, which would be the origin of macrofilaments [3]. In this communication the NMR, spectroscopic and X-ray results for the Cu(II), Cd(II) and Zn(II) complexes with the above mentioned ligands are discussed to establish possible binding modes of these ligands with metal ions. Both ligands are unstable in aqueous solution at pH>6 and their decomposition is additionally promoted by the presence of metal ions [4]. In acidic solution the AT ligand does not interact directly with the studied metal ions, but it acts as cation ATH +. The protonation site, established by X-ray technique, is the heterocyclic nitrogen which appears to be quite a basic donor. The most ‘destructive’ metal ion seems to be the cupric ion, which due to the redox reaction leads to several different decomposition products of AT, including SO 2− 4 and [NHCHNH 2] +Cl − [5]. The use of methanol solution makes possible the observation of the direct metal AT interaction before ligand decomposition. The X-ray and spectroscopic studies have shown that in both ligands the major coordination site is a heterocyclic nitrogen (for TP see also [6]). This similarity in metal ion binding by the heterocyclic nitrogen donor of both ligands and their possible chemical analogues could play a critical role in complex formation in lipid environment.