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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) | |
ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard | 100.164.932 |
MeSH | Paxilline |
PubChem CID | |
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]
Salvinorin A is the main active psychotropic molecule in Salvia divinorum. Salvinorin A is considered a dissociative hallucinogen.
The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-carbon compound isoprene and its derivatives called terpenes, diterpenes, etc. While sometimes used interchangeably with "terpenes", terpenoids contain additional functional groups, usually containing oxygen. When combined with the hydrocarbon terpenes, terpenoids comprise about 80,000 compounds. They are the largest class of plant secondary metabolites, representing about 60% of known natural products. Many terpenoids have substantial pharmacological bioactivity and are therefore of interest to medicinal chemists.
Terpenes are a class of natural products consisting of compounds with the formula (C5H8)n for n ≥ 2. Terpenes are major biosynthetic building blocks. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. In plants, terpenes and terpenoids are important mediators of ecological interactions, while some insects use some terpenes as a form of defense. Other functions of terpenoids include cell growth modulation and plant elongation, light harvesting and photoprotection, and membrane permeability and fluidity control.
Diterpenes are a class of terpenes composed of four isoprene units, often with the molecular formula C20H32. They are biosynthesized by plants, animals and fungi via the HMG-CoA reductase pathway, with geranylgeranyl pyrophosphate being a primary intermediate. Diterpenes form the basis for biologically important compounds such as retinol, retinal, and phytol. They are known to be antimicrobial and anti-inflammatory.
Indole-3-acetic acid is the most common naturally occurring plant hormone of the auxin class. It is the best known of the auxins, and has been the subject of extensive studies by plant physiologists. IAA is a derivative of indole, containing a carboxymethyl substituent. It is a colorless solid that is soluble in polar organic solvents.
Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ, as well as dehydrodolichol diphosphate.
Cyclopiazonic acid (α-CPA), a mycotoxin and a fungal neurotoxin, is made by the molds Aspergillus and Penicillium. It is an indole-tetramic acid that serves as a toxin due to its ability to inhibit calcium-dependent ATPases found in the endoplasmic and sarcoplasmic reticulum. This inhibition disrupts the muscle contraction-relaxation cycle and the calcium gradient that is maintained for proper cellular activity in cells.
Fusicoccins are organic compounds produced by a fungus. It has detrimental effect on plants and causes their death.
Penitrem A (tremortin) is an indole-diterpenoid mycotoxin produced by certain species of Aspergillus, Claviceps, and Penicillium, which can be found growing on various plant species such as ryegrass. Penitrem A is one of many secondary metabolites following the synthesis of paxilline in Penicillium crostosum. Penitrem A poisoning in humans and animals usually occurs through the consumption of contaminated foods by mycotoxin-producing species, which is then distributed through the body by the bloodstream. It bypasses the blood-brain barrier to exert its toxicological effects on the central nervous system. In humans, penitrem A poisoning has been associated with severe tremors, hyperthermia, nausea/vomiting, diplopia, and bloody diarrhea. In animals, symptoms of penitrem A poisoning has been associated with symptoms ranging from tremors, seizures, and hyperthermia to ataxia and nystagmus.
Momilactone B is an allelopathic agent produced from the roots of rice. It has been shown to be produced in high concentrations by the roots of rice seedlings. The production of momilactone B has also been induced in response to infection by blast fungus or irradiated with UV light. More recently it has been shown to be a potential chemotherapeutic agent against human colon cancer.
Lyngbyatoxin-a is a cyanotoxin produced by certain cyanobacteria species, most notably Moorea producens. It is produced as defense mechanism to ward off any would-be predators of the bacterium, being a potent blister agent as well as carcinogen. Low concentrations cause a common skin condition known as seaweed dermatitis.
Geraniol 8-hydroxylase (EC 1.14.14.83, Formerly EC 1.14.13.152, CYP76B6, G10H, CrG10H, SmG10H) is an enzyme with systematic name geraniol,NADPH:oxygen oxidoreductase (8-hydroxylating). This enzyme catalyses the following chemical reaction
ent-Sandaracopimaradiene synthase is an enzyme with systematic name ent-copalyl-diphosphate diphosphate-lyase [ent-sandaracopimara-8(14),15-diene-forming]. This enzyme catalyses the following chemical reaction
syn-Pimara-7,15-diene synthase is an enzyme with systematic name 9α-copalyl-diphosphate diphosphate-lyase (9β-pimara-7,15-diene-forming). This enzyme catalyses the following chemical reaction
Terpentetriene synthase is an enzyme with systematic name terpentedienyl-diphosphate diphosphate-lyase (terpentetriene-forming). This enzyme catalyses the following chemical reaction
Aphidicolan-16β-ol synthase (EC 4.2.3.42, PbACS) is an enzyme with systematic name 9α-copalyl-diphosphate diphosphate-lyase (aphidicolan-16β-ol-forming). This enzyme catalyses the following chemical reaction
Phyllocladan-16α-ol synthase (EC 4.2.3.45, PaDC1) is an enzyme with systematic name (+)-copalyl-diphosphate diphosphate-lyase (phyllocladan-16α-ol-forming). This enzyme catalyses the following chemical reaction
Fumitremorgins are tremorogenic metabolites of Aspergillus and Penicillium, that belong to a class of naturally occurring 2,5-diketopiperazines.
Penicillium paxilli is an anamorph, saprophytic species of the genus Penicillium which produces paxilline, paxisterol, penicillone, pyrenocine A, paspaline B and verruculogene. Penicillium paxilli is used as a model to study the biochemistry of the indol-diterepene biosynthesis
Lolitrem B is one of many toxins produced by a fungus called Epichloë festucae var. lolii), which grows in Lolium perenne. The fungus is symbiotic with the ryegrass; it doesn't harm the plant, and the toxins it produces kill insects that feed on ryegrass. Lolitrem B is one of these toxins, but it is also harmful to mammals. The shoots and flowers of infected ryegrass have especially high concentrations of lolitrem B, and when livestock eat too much of them, they get perennial ryegrass staggers. At low doses the animals have tremors, and at higher doses they stagger, and at higher yet doses the animals become paralyzed and die. The blood pressure of the animals also goes up. The effect of the lolitrem B comes on slowly and fades out slowly, as it is stored in fat after the ryegrass is eaten. The condition is especially common in New Zealand and Australia, and plant breeders there have been trying to develop strains of fungus that produce toxins only harmful to pests, and not to mammals.