Synthesis and Antinociceptive Profile of Novel Acidic Sulphonylhydrazone Derivatives From Natural Safrole

The synthesis and antinociceptive activity of new sulphonylhydrazone derivatives is described. The synthetic route started from safrole, an abundant Brazilian natural product which occurs in sassafras oil (Ocotea pretiosa). The active compounds were obtained by introducing an acidic moiety in the phenyl ring of the sulphonylhydrazone framework. The compounds were tested for analgesic and anti-inflammatory activity in the acetic acidinduced abdominal constriction and carrageenan-induced rat paw oedema tests, respectively. The most active analgesic was (4′-carboxybenzylidene) 6-methyl-3,4-methylene-dioxyphenylsulphonylhydrazide which was approximately 1.5-fold more potent than the standard dipyrone (52.4 vs 35.9% inhibition, respectively). The most active anti-inflammatory was the phenol compound (4′-hydroxy-3,5-ditert-butylbenzylidene) 6-methyl-3,4-methylenedioxyphenylsulphonylhydrazide (30% inhibition). The introduction of an acidic substituent in the phenyl ring of the sulphonylhydrazone moiety led to new lead compounds from safrole with analgesic and anti-inflammatory activity.