The synthesis, characterization and biological evaluation of a new nitric oxide donor agent

The synthesis of a new xanthine nitric oxide donor (TSP-81) is discussed. The designed compound included two structural moieties, i.e., theophylline (1,3-dimethylxanthine) and acetaminophen (4-hydroxyacetanilide), linked by the nitric oxide donor alkyl chain as a spacer. The compound was characterized by microanalysis (CHN), 1H-NMR, 13C-NMR, FT-IR and UV– –Vis spectroscopy and thermogravimetric analysis. The thermal behaviour showed that TSP-81 melts with decomposition in four steps, the most important ones being the 2nd one (the registered weight loss being 17.6 %) and the 3rd one (with a registered weight loss of 30.4 %). The toxicity degree, the anti-inflammatory effect and the ability of releasing nitric oxide of TSP-81 was also evaluated. The biological assays established that TSP-81 exhibits enhanced biological properties, such as lower toxicity and higher anti-inflammatory effect, compared to theophylline and acetaminophen, the drugs used as the parent molecules. Thus, TSP-81 is approximately 2 times more active than theophylline and 4 times more active than acetaminophen in reducing cotton pellet granuloma formation. Furthermore, the release of nitric oxide (NO) appears to play an important role in enhancing the anti-inflammatory effect.