1. ¹Department of Health Sciences, Universidad Pública de Navarra, Avda. Barañain, 31008 Pamplona, Spain
2. ²Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA
3. ³Department of Applied Chemistry, Universidad Pública de Navarra, Campus Arrosadía, 31006 Pamplona, Spain

Correspondence: Professor V Martínez-Merino, E-mail: merino@unavarra.es

Received 26 July 2004; Revised 9 December 2004; Accepted 9 December 2004; Published online 1 February 2005.

Abstract

Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and ability to inhibit a tumour-associated NADH oxidase (tNOX) activity of the plasma membrane has been described. To analyse the putative implication of tNOX in BTS-induced ROS generation, in this work we have synthesised and tested a new BTS derivative, the 6-[N-(2-phenylethyl)]benzo[b]thiophenesulphonamide 1,1-dioxide. According to its high lipophilicity, this compound showed a strong cytotoxic activity against a panel of six human tumour cell lines, including two human leukaemia (K-562 and CCRF-CEM) and four human solid tumours (HT-29, HTB54, HeLa and MEL-AC). We also tested the ability of this compound to inhibit the tNOX activity and we found an absolute dependence of this inhibition on the redox state of the tNOX: while under reducing conditions, that is, 100 mM GSH, the drug inhibits strongly the NOX activity with an EC₅₀ of about 0.1 nM, under oxidising conditions, there is no effect of the drug or just a slight stimulation of activity.