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| Names | |
|---|---|
| Preferred IUPAC name (2R,4bS,6aS,12bS,12cR,14aS)-4b-Hydroxy-2-(2-hydroxypropan-2-yl)-12b,12c-dimethyl-5,6,6a,7,12,12b,12c,13,14,14a-decahydro-2H-[1]benzopyrano[5′,6′:6,7]indeno[1,2-b]indol-3(4bH)-one | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.164.932 |
| MeSH | Paxilline |
| UNII | |
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| Properties | |
| C27H33NO4 | |
| Molar mass | 435.56 g/mol |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Paxilline is atoxic,tremorgenicditerpeneindolepolycyclicalkaloid molecule produced byPenicillium paxilliwhich was first characterized in 1975.[1][2] Paxilline is one of a class of tremorigenic mycotoxins, is apotassium channel blocker, and is potentiallygenotoxic.[3]
Paxilline was found to significantly extend the lifespan,healthspan, and mobility of agedC. elegans worms, but had no such effect on young worms.[4] Paxilline was not found to induce seizures when injected intracerebroventricularly in mice[5] but paradoxically had anticonvulsant activity againstpicrotoxin andpentylenetetrazol seizures in mice.[6] It has also been used in mice to induce autism-like behaviors through inhibition of theBK channel.[7]
Paxiline biosynthesis starts with the synthesis ofgeranylgeranyl pyrophosphate via theterpenoid pathway and indole-3-glycerol phosphate, which is an intermediate in thetryptophan biosynthesis pathway.[8] By expressing six genes known to be necessary for Paxilline synthesis inAspergillus oryzae, the further steps in the biosynthesis were identified; twoepoxidations and two cyclizations yieldpaspaline, then two oxidation reactions and a demethylation complete the synthesis.[9] This biosynthesis is notable for its unusual stereospecific polycyclization mechanism that has not been replicated in a chemical synthesis, though other mechanisms have been devised for total synthesis of Paxilline.[10] Paxilline has also been found to be mono- or di-prenylated withDMAPP by an atypical prenyltransferase enzyme.[11]
