title: Anti-inflammatory and antinociceptive activities of LQFM002 - A 4-nerolidylcatechol derivative.
abstract: OBJECTIVE
  The current study describes the synthesis and pharmacological evaluation of (E)-N-(3,7-dimethylocta-2,6-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.
  
  
  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-α 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.
  
  
  RESULTS
  LQFM002 inhibited PLA(2) activity, cell migration into the pleural cavity, and capillary permeability (Evan's blue concentration) and reduced TNF-α 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 μmol/kg naloxone (3mg/kg) reversed the analgesic effects of LQFM002 in the early phase of the formalin test.
  
  
  CONCLUSIONS
  LQFM002 showed anti-inflammatory activity, which possibly involved reduction of leukocyte migration and TNF-α levels. LQFM002 also demonstrated inhibition of PLA(2) activity in vitro. LQFM002 had an antinociceptive effect that involved the opioidergic system.
authors.affiliation: Institute of Biological Sciences, Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, Caixa Postal 131, CEP 74001-970, Goiânia, GO, Brazil. xico@icb.ufg.br
authors.forename: E A
authors.initials: EA
authors.lastname: Costa
authors.forename: R C
authors.initials: RC
authors.lastname: Lino
authors.forename: M N
authors.initials: MN
authors.lastname: Gomes
authors.forename: M V M
authors.initials: MV
authors.lastname: Nascimento
authors.forename: I F
authors.initials: IF
authors.lastname: Florentino
authors.forename: P M
authors.initials: PM
authors.lastname: Galdino
authors.forename: C H
authors.initials: CH
authors.lastname: Andrade
authors.forename: K R
authors.initials: KR
authors.lastname: Rezende
authors.forename: L O
authors.initials: LO
authors.lastname: Magalhães
authors.forename: R
authors.initials: R
authors.lastname: Menegatti
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan / Q000633:toxicity; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C110583:4-nerolidylcatechol; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D002396:Catechols; C579156:LQFM002; D064801:Phospholipase A2 Inhibitors; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan; D054467:Phospholipases A2