Biol. Pharm. Bull. 29(6) 1180—1185 (2006)

line therapeutic agents for the treatment of arthritis. NSAID’s reduce the pain and swelling associated with arthritis by blocking the metabolism of arachidonic acid (AA) through the enzyme cyclooxygenase (COX) and thereby the production of prostaglandins, e.g. PGE2, which sensitizes nociceptors at nerve fiber terminals. Additionally, the 5-lipoxygenase (5-LO) products such as leukotriene B4 (LTB4) also contributes to the hyperalgesia seen during inflammation by decreasing the mechanical and thermal thresholds of C fiberes. Leukotrienes, especially LTB4 together with prostaglandins are implicated in the acute ulceration induced by NSAID’s. For these reasons, compounds that achieve dual inhibition of enzymes COX and 5LO reduce side effects and improved efficacy in the combat of pain in inflammatory diseases. Some evidences suggest that the hydrazone moiety present in phenylhydrazone derivative 1 (Fig. 1), possesses a pharmacophoric character for the inhibition of COX and hydrazone type containing compounds such as compound 2 (Fig. 1) were described as dual COX/5-LO inhibitors. According to these evidences, there are some reports about synthesis and pharmacological evaluation of new bioactive compounds with N-aroylarylhydrazone structure acting at the AA cascade enzyme level (Fig. 2, compounds 3—5). On the basis of these reports, we described previously the synthesis and analgesic profile of Narylhydrazone derivatives of mefenamic acid 6 (Fig. 3), a known NSAID drug with fenamate structure. Most of these synthesized compounds were effective as analgesic agents in comparison to control and showed more analgesic activity in comparison to mefenamic acid. In fact, compound 7 (Fig. 3) displayed 3.6-fold greater potency than mefenamic acid as an analgesic agent, in a model of abdominal constrictions induced by acetic acid. These results led us to design new structurally related derivatives 10, 11. Target compounds 10, 11 were obtained according to Chart 1. The starting hydrazides 8 (X O, R H and X NH, R H) were prepared by the known procedures and hydrazide 8 (X O, R Cl) was synthesized as described previously. Compounds 10, 11 were synthesized by acid-catalyzed condensation of hydrazides 8 with corresponding substituted benzaldehydes or acetophenones. The synthesis and antimicrobial activity 1180 Vol. 29, No. 6 Biol. Pharm. Bull. 29(6) 1180—1185 (2006)