2-hydroxy-1-naphthaldehyde 2-methylthiosemicarbazone.

Ligands of the aroylhydrazone class have shown much promise as potential chelators for treatment of iron overload disease and perhaps cancer (Johnson et al., 1982; Baker et al., 1992; Richardson et al., 1995; Richardson & Milnes, 1997). Our previous investigations have demonstrated that 2-hydroxy-1naphthaldehyde isonicotinoyl hydrazone, (II), and several other aroylhydrazone chelators possess antitumour activity due to their ability to bind intracellular iron (Richardson et al., 1995; Richardson & Milnes, 1997; Darnell & Richardson, 1999; Richardson & Bernhardt, 1999). From these studies we have been able to identify structural components of the hydrazones which infer antineoplastic activity, namely the salicylaldehyde and 2-hydroxy-1-naphthaldehyde moieties (Richardson et al., 1995). Another related group of chelators known as the thiosemicarbazones also show high antitumour activity due to their ability to inhibit ribonucleotide reductase (Cory et al., 1995; Liu et al., 1995). Considering this, we have designed and synthesized a new group of ligands by condensation of salicylaldehyde and 2-hydroxy-1-naphthaldehyde with a range of thiosemicarbazides. The parent compound of this new series of chelators is 2-hydroxy-1-naphthaldehyde thiosemicarbazone, (III). Substitution of a methyl group at the 2-position of (III) to give (I) results in a marked decrease in anti-proliferative activity and a decrease in iron chelation ef®cacy (Lovejoy et al., 1999). These data may suggest that this latter substitution diminishes the metal ion binding capability of these chelators. Studies assessing the biological activity of this new class of compounds are underway and will be reported elsewhere (Lovejoy et al., 1999). In the present communication we report the X-ray crystal structure of 2-hydroxy-1-naphthaldehyde 2-methylthiosemicarbazone, (I).