Anti-inflammatory and antinociceptive activities of LQFM002 - A 4-nerolidylcatechol derivative

作者：Costa E A^*; Lino R C; Comes M N; Nascimento M V M; Fiorentino I F; Galdino P M; Andrade C H; Rezehde K R; Magalhaes L O; Menegatti R

来源：Life Sciences, 2013, 92(3): 237-244.

DOI：10.1016/j.lfs.2012.12.003

• Antinociception
• Anti-inflammatory
• PLA(2) activity
• TNF-alpha

Aims: The current study describes the synthesis and pharmacological evaluation of (E)-N-(3,7-dimethylocta2,6-dienyl)-1,3-dimethyl-1H-pyrazol-5-amine (LQFM002), a compound originally designed through a molecular simplification strategy from 4-nerolidylcatechol. LQFM002 was evaluated for preservation of the PLA(2) enzyme inhibitory effects of the lead compound, 4-nerolidylcatechol, using in vitro and in vivo models.
Main methods: Rota-rod, open field and pentobarbital-induced sleeping tests were used to evaluate the effects of LQFM002 on the central nervous system. A gel plate assay of PLA(2) activity, carrageenan-induced pleurisy and TNF-alpha levels was used to assay anti-inflammatory activity. Antinociceptive activities of LQFM002 were evaluated with acetic acid-induced writhing, formalin and hot-plate tests, while involvement of the opioid pathway in the LQFM002 antinociceptive effect was investigated with naloxone pre-treatment.
Key findings: LQFM002 inhibited PLA(2) activity, cell migration into the pleural cavity, and capillary permeability (Evan's blue concentration) and reduced TNF-alpha levels in pleural exudates. LQFM002 also reduced acetic acid-induced writhing and the licking time in both phases of the formalin test and increased latency in the hot-plate test. Pre-treatment with 8.25 mu mol/kg naloxone (3 mg/kg) reversed the analgesic effects of LQFM002 in the early phase of the formalin test.
Significance: LQFM002 showed anti-inflammatory activity, which possibly involved reduction of leukocyte migration and TNF-alpha levels. LQFM002 also demonstrated inhibition of PLA(2) activity in vitro. LQFM002 had an antinociceptive effect that involved the opioidergic system.

• 出版日期2013-2-27