Monoamine oxidase inhibitory activities of indolylalkaloid toxins from the venom of the colonial spider Parawixia bistriata: Functional characterization of PwTX-I

Autor(es)

Saidemberg, Daniel M. ^[1] ; Ferreira, Marco A. B. ^[2] ; Takahashi, Tatiane N. ^[1] ; Gomes, Paulo C. ^{[1, 3]} ; Cesar-Tognoli, Lilian M. M. ^[1] ; da Silva-Filho, Luiz C. ^[4] ; Tormena, Claudio F. ^[5] ; da Silva, Gil V. J. ^[2] ; Palma, Mario S. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, UNESP, Inst Biosci, Dept Biol, CEIS, Lab Struct Biol & Zoochem, BR-13506900 Rio Claro, SP - Brazil

^[2] Univ Sao Paulo, FFCLRP, Dept Chem, BR-14040901 Ribeirao Preto, SP - Brazil

^[3] Ezequiel Dias Fdn FUNED, Directory Res & Dev, BR-30510010 Belo Horizonte, MG - Brazil

^[4] Sao Paulo State Univ, UNESP, Fac Sci, Dept Chem, BR-17033360 Sao Paulo - Brazil

^[5] Univ Estadual Campinas, Inst Chem, BR-13084971 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 54, n. 6, p. 717-724, NOV 2009.
• Citações Web of Science: 15

Resumo

Colonial spiders evolved a differential prey-capture behaviour in concert with their venom chemistry, which may be a source of novel drugs. Some highly active tetrahydro-beta-carboline (TH beta C) toxins were recently isolated from the venom of the colonial spider Parawixia bistriata; the spiders use these toxins as part of their chemical arsenal to kill and/or paralyze preys. The major TH beta C compound isolated from this venom was identified as 6-hydroxytrypargine, also known as PwTX-I. Most natural compounds of animal origin occur in low abundance, and the natural abundance of PwTX-I is insufficient for complete functional characterization. Thus, PwTx-I was synthesized using a Pictet-Spengler condensation strategy, and the stereoisomers of the synthetic toxin were separated by chiral chromatography. The fraction of venom containing a mixture of three natural TH beta C toxins and enantiomers of PwTx-I were analyzed for inhibition of monoamine oxidase (MAO)-A and -B and for toxicity to insects. We reveal that the mixture of the natural TH beta C toxins, as well as the enantiomers of PwTx-I, were non-competitive inhibitors of MAO-A and MAO-B and caused potent paralysis of honeybees. The (-)-PwTX-I enantiomer is 2-fold more potent than the (+)-PwTX-I enantiomer in the assays performed. (C) 2009 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 06/57122-7 - Procura de compostos líderes para o desenvolvimento racional de novos fármacos e pesticidas a partir bioprospecção da fauna de artrópodes brasileiros
• Beneficiário: Mario Sergio Palma
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 06/50158-6 - Estudos sobre a sintese total de um novo espiro-glicosideo isolado do veneno da vespa polybia paulista (hymenoptera, vespidae) visando sua bioprospeccao.
• Beneficiário: Luiz Carlos da Silva Filho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 04/07942-2 - A bioprospecção da fauna de artrópodes do estado de São Paulo pela procura de compostos-líderes para o desenvolvimento racional de novos fármacos e pesticidas seletivos
• Beneficiário: Mario Sergio Palma
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular