Synthesis and evaluation of analgesic, antiinflammatory and antiplatelet properties of new 2-pyridylarylhydrazone derivatives

Article abstract of DOI:10.1016/S0223-5234(98)80008-1

This work describes recent results from our research program aiming at the synthesis and pharmacological evaluation of new compounds acting as antiinflammatory, analgesic and platelet antiaggregatory. In this paper the synthesis and the pharmacological profile as analgesic, antiinflammatory and anti-platelet of new functionalized 2-pyridylarylhydrazone derivatives 5a-r are discussed. This class of N-heterocyclic derivatives represents a new series of prototype candidates with analgesic and antiinflammatory properties possessing also an important anti-aggregating activity. The pharmacological results herein disclosed suggest that the anti-inflammatory and analgesic activities of these new pyridynehydrazone derivatives observed in the carrageenan pleurisy model and acetic acid writhing test, respectively, is probably due to an interference on the arachidonic acid (AA) metabolism. The most important antiinflammatory derivative 2-(2-formylfurane)pyridylhydrazone 5p presented a 79% inhibition of pleurisy at a dose of 80.1 μmol/kg. We also described the results concerning the mechanism of action of this series of N-heterocyclic derivatives in platelet aggregation which suggest a Ca²⁺ participation, probably by a complexation scavenger mechanism. Compound 2-(2-formylfurane)pyridylhydrazone 5p was able to complex Ca²⁺ in in vitro experiments at 100 μM concentration, indicating that this series of compounds can act as Ca²⁺ scavenger depending on the nature of the aryl moiety present at the imine subunit.