title: Anti-inflammatory properties of convolutamydine A and two structural analogues.
abstract: OBJECTIVE
  Convolutamydine A is an oxindole alkaloid that can be isolated from a marine bryozoan. Due to the variety of biological effects, two analogues were synthesized and their anti-inflammatory properties were evaluated.
  
  
  METHODS
  The anti-inflammatory effects of convolutamydine A and its analogues (ISA003 and ISA147) were investigated in a formalin-induced licking behaviour model, where mice received an intraplantar injection of formalin and their licking behaviour was evaluated for 30min. Additionally, inflammatory parameters were evaluated in a subcutaneous air pouch (SAP) model of carrageenan-induced inflammation. Exudates were collected for leukocyte counts; measurement of protein, prostaglandin E2 (PGE2) and cytokines by ELISA; and analysis of nitric oxide (NO) using a nitrate conversion protocol. Cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) from RAW 264.7 cells were quantified by immunoblotting.
  
  
  RESULTS
  Convolutamydine A and its two analogues inhibited the formalin-induced licking response at doses as low as 0.01mg/kg. An inhibitory effect was also observed on leukocyte migration and the production of NO, PGE2 and cytokines (IL-6 and TNF-α). The reduction in inflammatory parameters did not appear to be correlated with a direct reduction in the number of cells in the SAP, because a reduction in NO and PGE2 production by cultured macrophages was observed in addition to the inhibition of iNOS and COX2 enzyme expression.
  
  
  CONCLUSIONS
  These results indicate that convolutamydine A and its two analogues have significant anti-inflammatory effects. These substances can be improved to generate lead compounds for the synthesis of new anti-inflammatory drugs.
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Av. Carlos Chagas Filho, 373. Prédio do CCS, bloco J, sala 10, 21941-902 Rio de Janeiro, Brazil. Electronic address: patricia.dias@icb.ufrj.br.
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Fernandes
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Av. Carlos Chagas Filho, 373. Prédio do CCS, bloco J, sala 10, 21941-902 Rio de Janeiro, Brazil.
authors.forename: Renata S
authors.initials: RS
authors.lastname: Zardo
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Av. Carlos Chagas Filho, 373. Prédio do CCS, bloco J, sala 10, 21941-902 Rio de Janeiro, Brazil.
authors.forename: Gabriella S M
authors.initials: GS
authors.lastname: Figueiredo
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, Brazil.
authors.forename: Bárbara V
authors.initials: BV
authors.lastname: Silva
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Química, Rio de Janeiro, Brazil.
authors.forename: Angelo C
authors.initials: AC
authors.lastname: Pinto
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002351:Carrageenan / Q000633:toxicity; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C533541:convolutamydine A; D005557:Formaldehyde; D009569:Nitric Oxide; D007510:Isatin; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: Anti-inflammatory drugs; Convolutamydine A; Inflammation; Isatin