The synthesis of a new xanthine nitric oxide donor (TSP-81) has been
discussed. The designed compound includes two structural moieties -
theophylline (1,3-dimethylxanthine) and acetaminophen (4-hydroxyacetanilide)
linked by the nitric oxide donor alkyl chain as a spacer. The compound has
been characterized by microanalysis (CHN), 1H-NMR, 13C-NMR, FT-IR, UV-vis, TG
and DTG. 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 the TSP-81 have also been evaluated. The biological
assays established that TSP-81 exhibits enhanced biological properties such
as lower toxicity and higher anti-inflammatory effect in reference with
theophylline and acetaminophen, the drugs used as parents molecules. The
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 have an important
contribution to enhancing the anti-inflammatory effect.
The synthesis, characterization and biological evaluation of a new nitric oxide donor agent