SYNTHESIS AND EVALUATION OF ANALGESIC, ANTIINFLAMMATORY AND ANTIPLATELET PROPERTIES OF NEW 2-PYRIDYLARYLHYDRAZONE DERIVATIVES

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 p aper the synthesis and the pharmacological profile as analgesic, antii nflammatory and anti-platelet of new functionalized 2-pyridylarylhydra zone derivatives 5a-r are discussed. This class of N-heterocyclic deri vatives represents a new series of prototype candidates with analgesic and antiinflammatory properties possessing also an important anti-agg regating activity. The pharmacological results herein disclosed sugges t that the antiinflammatory and analgesic activities of these new pyri dynehydrazone derivatives observed in the carrageenan pleurisy model a nd acetic acid writhing test, respectively is probably due to an inter ference on the arachidonic acid (AA) metabolism. The most important an tiinflammatory derivative 2-(2-formylfurane)pyridylhydrazone 5p presen ted a 79% inhibition of pleurisy at a dose of 80.1 mu mol/kg. We also described the results concerning the mechanism of action of this serie s 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 mu M concentration, indicating that t his series of compounds can act as Ca2+ scavenger depending on the nat ure of the aryl moiety present at the imine subunit. (C) Elsevier, Par is.