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| Names | |
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| 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) |
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| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.164.932 
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| MeSH | Paxilline |
PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C27H33NO4 | |
| Molar mass | 435.56 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
Paxilline is a toxic, tremorgenic diterpene indole polycyclic alkaloid molecule produced by Penicillium paxilli which was first characterized in 1975.[1][2] Paxilline is one of a class of tremorigenic mycotoxins, is a potassium channel blocker, and is potentially genotoxic.[3]
Paxilline was found to significantly extend the lifespan, healthspan, and mobility of aged C. 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 against picrotoxin and pentylenetetrazol seizures in mice.[6] It has also been used in mice to induce autism-like behaviors through inhibition of the BK channel.[7]
Paxiline biosynthesis starts with the synthesis of geranylgeranyl pyrophosphate via the terpenoid pathway and indole-3-glycerol phosphate, which is an intermediate in the tryptophan biosynthesis pathway.[8] By expressing six genes known to be necessary for Paxilline synthesis in Aspergillus oryzae, the further steps in the biosynthesis were identified; two epoxidations and two cyclizations yield paspaline, 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 with DMAPP by an atypical prenyltransferase enzyme.[11]
