Paxilline

Source: Wikipedia, the free encyclopedia.
Not to be confused with the protein Paxillin.
Paxilline
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
ECHA InfoCard
 100.164.932 Edit this at Wikidata
MeSH Paxilline
UNII
  • InChI=1S/C27H33NO4/c1-24(2,30)23-20(29)14-18-21(32-23)10-11-25(3)26(4)15(9-12-27(18,25)31)13-17-16-7-5-6-8-19(16)28-22(17)26/h5-8,14-15,21,23,28,30-31H,9-13H2,1-4H3/t15-,21-,23-,25+,26+,27+/m0/s1 checkY
    Key: ACNHBCIZLNNLRS-UBGQALKQSA-N checkY
  • InChI=1/C27H33NO4/c1-24(2,30)23-20(29)14-18-21(32-23)10-11-25(3)26(4)15(9-12-27(18,25)31)13-17-16-7-5-6-8-19(16)28-22(17)26/h5-8,14-15,21,23,28,30-31H,9-13H2,1-4H3/t15-,21-,23-,25+,26+,27+/m0/s1
    Key: ACNHBCIZLNNLRS-UBGQALKQBX
  • O=C5/C=C6/[C@]4(O)CC[C@H]3Cc2c1ccccc1[nH]c2[C@@]3([C@]4(CC[C@@H]6O[C@@H]5C(O)(C)C)C)C
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).
☒N verify (what is checkY☒N ?)

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,

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]

Biosynthesis

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]

Sources and references

  1. ^ Paxilline product page from Fermentek
  2. ISSN 0040-4039
    .
  3. ISBN 9780128114100
    .
  4. PMID 30613772
    .
  5. S2CID 140209807
    .
  6. S2CID 14129074
    .
  7. S2CID 232300623
    – via APA PsycArticles.
  8. PMID 15281747
    .
  9. PMID 23311903
    .
  10. PMID 33596652
    .
  11. S2CID 253767473
    .
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