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

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-β-carboline (THβC) 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 THβC 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 THβC 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 THβC 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.