Heterocyclic NO-donors as anti-cancer agents

Abstract

Nitric oxide (NO) is involved in numerous biological processes including cancer, where this small diatomic radical can exert both pro- and anti-cancer effects. Two series of novel NO-donors were synthesised in this work, the first representing an extension to the S-nitrosothiols (RSNO) class, with the second utilising the popular 1,2,5-oxadiazole-2-oxide (furoxan) functionality. The oxathiazolylium-5-olates 39a, 39f, 39h-D, were successfully made via improved seven-step synthesis whilst a series of combretastatin-like furoxans 144a-c (NO-hybrids) were generated in a one-pot reaction. All compounds; including byproducts from failed alternative synthetic routes, had their cytotoxic activity evaluated. From this study NO-hybrid 144c showed the most promising biological profile when tested against eight different ovarian cancer cell lines.