title: Monoamine oxidase inhibitory activities of indolylalkaloid toxins from the venom of the colonial spider Parawixia bistriata: functional characterization of PwTX-I.
abstract: 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 (THbetaC) 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 THbetaC 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 THbetaC 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 THbetaC 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.
authors.affiliation: Department of Biology/CEIS, Laboratory Structural Biology and Zoochemistry, Institute of Biosciences, São Paulo State University (UNESP), Avenue 24A 1515, Bela Vista, CEP 13506-900, Rio Claro, SP, Brazil.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Saidemberg
authors.forename: Marco A B
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Tatiane N
authors.initials: TN
authors.lastname: Takahashi
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Gomes
authors.forename: Lilian M M
authors.initials: LM
authors.lastname: Cesar-Tognoli
authors.forename: Luiz C
authors.initials: LC
authors.lastname: da Silva-Filho
authors.forename: Cláudio F
authors.initials: CF
authors.lastname: Tormena
authors.forename: Gil V J
authors.initials: GV
authors.lastname: da Silva
authors.forename: Mario S
authors.initials: MS
authors.lastname: Palma
mesh_terms: D000818:Animals; D026121:Indole Alkaloids / Q000302:isolation & purification / Q000633:toxicity*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013111:Spider Venoms / Q000737:chemistry*; D013112:Spiders; D013237:Stereoisomerism
chemical_list: D026121:Indole Alkaloids; D008996:Monoamine Oxidase Inhibitors; D013111:Spider Venoms; D008995:Monoamine Oxidase