Hypericin

Last updated
Hypericin [1]
Hypericin2DACS.svg
Hypericin 3D ball.png
Names
Preferred IUPAC name
1,3,4,6,8,13-Hexahydroxy-10,11-dimethylphenanthro[1,10,9,8-opqra]perylene-7,14-dione
Other names
4,5,7,4',5',7'-Hexahydroxy-2,2'-dimethylnaphthodianthrone
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.008.129 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C30H16O8/c1-7-3-9(31)19-23-15(7)16-8(2)4-10(32)20-24(16)28-26-18(12(34)6-14(36)22(26)30(20)38)17-11(33)5-13(35)21(29(19)37)25(17)27(23)28/h3-6,31-36H,1-2H3 Yes check.svgY
    Key: BTXNYTINYBABQR-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C30H16O8/c1-7-3-9(31)19-23-15(7)16-8(2)4-10(32)20-24(16)28-26-18(12(34)6-14(36)22(26)30(20)38)17-11(33)5-13(35)21(29(19)37)25(17)27(23)28/h3-6,31-36H,1-2H3
    Key: BTXNYTINYBABQR-UHFFFAOYAC
  • Cc0cc(O)c1C(=O)c2c(O)cc(O)c3c2c4c1c0c5c6c4c7c3c(O)cc(O)c7C(=O)c6c(O)cc5C
Properties
C30H16O8
Molar mass 504.450 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Hypericin is a naphthodianthrone, an anthraquinone derivative which, together with hyperforin, is one of the principal active constituents of Hypericum (Saint John's wort). [2] [3] Hypericin is believed to act as an antibiotic, antiviral [2] and non-specific kinase inhibitor. Hypericin may inhibit the action of the enzyme dopamine β-hydroxylase, leading to increased dopamine levels,[ citation needed ] although thus possibly decreasing norepinephrine and epinephrine.

It was initially believed[ according to whom? ] that the anti-depressant pharmacological activity of hypericin was due to inhibition of monoamine oxidase enzyme. The crude extract of Hypericum is a weak inhibitor of MAO-A and MAO-B. [4] [5] Isolated hypericin does not display this activity, but does have some affinity for NMDA receptors.[ citation needed ] This points in the direction that other constituents are responsible for the MAOI effect. The current belief is that the mechanism of antidepressant activity is due to the inhibition of re-uptake of certain neurotransmitters. [2]

The large chromophore system in the molecule means that it can cause photosensitivity when ingested beyond threshold amounts.[ citation needed ] Photosensitivity is often seen in animals that have been allowed to graze on St. John's Wort.[ citation needed ] Because hypericin accumulates preferentially in cancerous tissues, it is also used as an indicator of cancerous cells.[ citation needed ] In addition, hypericin is under research as an agent in photodynamic therapy, whereby a biochemical is absorbed by an organism to be later activated with spectrum-specific light from specialized lamps or laser sources, for therapeutic purposes.[ citation needed ] The antibacterial and antiviral effects of hypericin are also believed to arise from its ability for photo-oxidation of cells and viral particles. [2]

Hypericin derives from cyclisation of polyketides. [6] [7]

The biosynthesis of hypericins is through the polyketide pathway where an octaketide chain goes through successive cyclizations and decarboxylations to form emodin anthrone which is believed to be the precursor of hypericin. Oxidization reactions yield protoforms which then are converted into hypericin and pseudohypericin. These reactions are photosensitive and take place under exposure to light and using the enzyme Hyp-1. [8] [9] [10] [11] [12]

Related Research Articles

<i>Hypericum perforatum</i> Flowering plant in the St Johns wort family Hypericaceae

Hypericum perforatum, commonly known as St John's wort, is a flowering plant in the family Hypericaceae. It is a perennial plant that grows up to one meter tall, with many yellow flowers that have clearly visible black glands around their edges, long stamens, and three pistils. Probably a hybrid between the closely related H. attenuatum and H. maculatum that originated in Siberia, the species is now found worldwide. It is native to temperate regions across Eurasia and North Africa, and has been introduced to East Asia, Australia, New Zealand, and parts of North and South America. In many areas where it is not native, H. perforatum is considered a noxious weed. It densely covers open areas to the exclusion of native plants, and is poor grazing material. As such, methods for biocontrol have been introduced in an attempt to slow or reverse the spread of the species.

<i>Hypericum</i> Genus of flowering plants known as St. Johns worts

Hypericum is a genus of flowering plants in the family Hypericaceae. The genus has a nearly worldwide distribution, missing only from tropical lowlands, deserts and polar regions. Many Hypericum species are regarded as invasive species and noxious weeds. All members of the genus may be referred to as St. John's wort, and some are known as goatweed. The white or pink flowered marsh St. John's worts of North America and eastern Asia are generally accepted as belonging to the separate genus TriadenumRaf.

<i>Hypericum calycinum</i> Species of flowering plant in the St Johns wort family Hypericaceae

Hypericum calycinum is a species of prostrate or low-growing shrub in the flowering plant family Hypericaceae. Widely cultivated for its large yellow flowers, its names as a garden plant include Rose-of-Sharon in Britain and Australia, and Aaron's beard, great St-John's wort, creeping St. John's wort and Jerusalem star. Grown in Mediterranean climates, widely spread in the Strandja Mountains along the Bulgarian and Turkish Black Sea coast.

<span class="mw-page-title-main">Hyperforin</span> Chemical compound

Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum. Hyperforin may be involved in the pharmacological effects of St. John's wort, specifically in its antidepressant effects.

<span class="mw-page-title-main">Dimethylallyl pyrophosphate</span> Chemical compound

Dimethylallyl pyrophosphate is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynthesis. It is an isomer of isopentenyl pyrophosphate (IPP) and exists in virtually all life forms. The enzyme isopentenyl pyrophosphate isomerase catalyzes isomerization between DMAPP and IPP.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.

<span class="mw-page-title-main">Epothilone</span> Class of chemical compounds

Epothilones are a class of potential cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials, epothilones have better efficacy and milder adverse effects than taxanes.

An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor or leukotriene receptor antagonist and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in asthma and COPD. Leukotriene receptor antagonists are sometimes colloquially referred to as leukasts.

Arachidonate 5-lipoxygenase inhibitors are compounds that slow or stop the action of the arachidonate 5-lipoxygenase enzyme, which is responsible for the production of inflammatory leukotrienes. The overproduction of leukotrienes is a major cause of inflammation in asthma, allergic rhinitis, and osteoarthritis.

<span class="mw-page-title-main">Monoamine oxidase B</span> Protein-coding gene in the species Homo sapiens

Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene.

<span class="mw-page-title-main">Reuptake inhibitor</span> Type of drug

Reuptake inhibitors (RIs) are a type of reuptake modulators. It is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.

<span class="mw-page-title-main">Adhyperforin</span> Chemical compound

Adhyperforin is a phytochemical found in the members of the plant genus Hypericum including St. John's Wort. It has a very similar pharmacological profile to hyperforin and acts as a TRPC6 ion channel activator, thereby inhibiting the reuptake of various neurotransmitters including serotonin, norepinephrine, dopamine, GABA, and glutamate. Adhyperforin is found in St. John's Wort in levels approximately 1/10 those of hyperforin.

<span class="mw-page-title-main">Betaenone B</span> Chemical compound

Betaenone B, like other betaenones, is a secondary metabolite isolated from the fungus Pleospora betae, a plant pathogen. Its phytotoxic properties have been shown to cause sugar beet leaf spots, which is characterized by black, pycnidia containing, concentric circles eventually leading to necrosis of the leaf tissue. Of the seven phytotoxins isolated in fungal leaf spots from sugar beet, betaenone B showed the least amount of phytotoxicity showing only 8% inhibition of growth while betaenone A and C showed 73% and 89% growth inhibition, respectively. Betaenone B is therefore not considered toxic to the plant, but will produce leaf spots when present in high concentrations (0.33 μg/μL). While the mechanism of action of betaenone B has yet to be elucidated, betaenone C has been shown to inhibit RNA and protein synthesis. Most of the major work on betaenone B, including the initial structure elucidation of betaenone A, B and C as well as the partial elucidation mechanism of biosynthesis, was presented in three short papers published between 1983 and 1988. The compounds were found to inhibit a variety of protein kinases signifying a possible role in cancer treatment.

<span class="mw-page-title-main">Dynamic combinatorial chemistry</span>

Dynamic combinatorial chemistry (DCC); also known as constitutional dynamic chemistry (CDC) is a method to the generation of new molecules formed by reversible reaction of simple building blocks under thermodynamic control. The library of these reversibly interconverting building blocks is called a dynamic combinatorial library (DCL). All constituents in a DCL are in equilibrium, and their distribution is determined by their thermodynamic stability within the DCL. The interconversion of these building blocks may involve covalent or non-covalent interactions. When a DCL is exposed to an external influence, the equilibrium shifts and those components that interact with the external influence are stabilised and amplified, allowing more of the active compound to be formed.

<i>Hypericum olympicum</i> Species of flowering plant in the St Johns wort family Hypericaceae

Hypericum olympicum, commonly known as the Mount Olympus St. John's wort, is a species of flowering plant in the family Hypericaceae found in the Balkans and Turkey and introduced to western Europe. It has been widely cultivated for centuries because of its large, showy flowers, which are far larger than those of most other species in Hypericum.

<span class="mw-page-title-main">Amentoflavone</span> Chemical compound

Amentoflavone is a biflavonoid constituent of a number of plants including Ginkgo biloba, Chamaecyparis obtusa (hinoki), Biophytum sensitivum, Selaginella tamariscina, Hypericum perforatum and Xerophyta plicata.

<span class="mw-page-title-main">Callystatin A</span> Chemical compound

Callystatin A is a polyketide natural product from the leptomycin family of secondary metabolites. It was first isolated in 1997 from the marine sponge Callyspongia truncata which was collected from the Goto Islands in the Nagasaki Prefecture of Japan by the Kobayashi group. Since then its absolute configuration has been elucidated and callystatin A was discovered to have anti-fungal and anti-tumor activities with extreme potency against the human epidermoid carcinoma KB cells (IG50 = 10 pg/ml) and the mouse lymphocytic leukemia Ll210 cells (IG50 = 20 pg/ml).

<span class="mw-page-title-main">Atrop-abyssomicin C</span> Chemical compound

Atrop-abyssomicin C is a polycyclic polyketide-type natural product that is the atropisomer of abyssomicin C. It is a spirotetronate that belongs to the class of tetronate antibiotics, which includes compounds such as tetronomycin, agglomerin, and chlorothricin. In 2006, the Nicolaou group discovered atrop-abyssomicin C while working on the total synthesis of abyssomicin C. Then in 2007, Süssmuth and co-workers isolated atrop-abyssomicin C from Verrucosispora maris AB-18-032, a marine actinomycete found in sediment of the Japanese sea. They found that atrop-abyssomicin C was the major metabolite produced by this strain, while abyssomicin C was a minor product. The molecule displays antibacterial activity by inhibiting the enzyme PabB, thereby depleting the biosynthesis of p-aminobenzoate.

<i>Hypericum bupleuroides</i> Species of flowering plant in the St Johns wort family Hypericaceae

Hypericum bupleuroides is a species of perennial flowering plant in the St John's wort family, Hypericaceae. It grows 45–80 centimeters tall, and notably has perfoliate leaves that are fused at the stem. It has pyramid-shaped flower clusters of 1 to 25 flowers with yellow petals in a star-shaped arrangement. The species is found along the Black Sea coast near the Turkish–Georgian border. Hypericum bupleuroides has a small distribution and specific habitat requirements that make it vulnerable to environmental pressures.

<span class="mw-page-title-main">Pseudohypericin</span> Chemical compound

Pseudohypericin is an aromatic polycyclic dione that is very closely related to hypericin. It is found most commonly in the St. John's wort family of plants, namely in Hypericum perforatum. In preliminary studies in animal models, pseudohypericin has shown antiviral effects. It may also contribute to the potential antidepressant effect of Hypericum perforatum extracts.

References

  1. Merck Index , 11th Edition, 4799
  2. 1 2 3 4 Mehta S (2012-12-18). "Pharmacognosy of St. John's Wort". Pharmaxchange.info. Retrieved 2014-02-16.
  3. Oubre A (1991). "Hypericin: the active ingredient in Saint John's Wort". Archived from the original on September 28, 2007. Retrieved September 18, 2006.
  4. Thiede HM, Walper A (October 1994). "Inhibition of MAO and COMT by hypericum extracts and hypericin". Journal of Geriatric Psychiatry and Neurology. 7 (Suppl 1): S54–56. doi:10.1177/089198879400700114. ISSN   0891-9887. PMID   7857510. S2CID   208042437.
  5. Bladt S, Wagner H (October 1994). "Inhibition of MAO by fractions and constituents of hypericum extract". Journal of Geriatric Psychiatry and Neurology. 7 (Suppl 1): S57–59. doi:10.1177/089198879400700115. ISSN   0891-9887. PMID   7857511. S2CID   23531061.
  6. Loren W. Walker (1999). "A Review of the Hypothetical Biogenesis and Regulation of Hypericin synthesis via the Polyketide Pathway in Hypericum perforatum and Experimental Methods Proposed to Evaluate the Hypothesis". Archived from the original on 2019-06-26. Retrieved 2011-01-04.{{cite journal}}: Cite journal requires |journal= (help)
  7. Christian Hertweck (2009). "Polyketide Biosynthesis". Angew. Chem. Int. Ed. 48 (26): 4688–4716. doi:10.1002/anie.200806121. PMID   19514004.
  8. Karioti A, Bilia AR (2010). "Hypericins as potential leads for new therapeutics". Int J Mol Sci. 11 (2): 562–594. doi: 10.3390/ijms11020562 . PMC   2852855 . PMID   20386655.
  9. Falk H (1999). "From the Photosensitizer Hypericin to the Photoreceptor Stentorin- The Chemistry of Phenanthroperylene Quinones". Angew. Chem. Int. Ed. Engl. 38 (21): 3116–3136. doi:10.1002/(SICI)1521-3773(19991102)38:21<3116::AID-ANIE3116>3.0.CO;2-S. PMID   10556884.
  10. Bais HP, Vepachedu R, Lawrence CB, Stermitz FR, Vivanco JM (2003). "Molecular and biochemical characterization of an enzyme responsible for the formation of hypericin in St. John's wort (Hypericum perforatum L.)". J. Biol. Chem. 278 (34): 32413–32422. doi: 10.1074/jbc.M301681200 . PMID   12799379.
  11. Michalska K, Fernandes H, Sikorski M, Jaskolski M (2010). "Crystal structure of Hyp-1, a St. John's wort protein implicated in the biosynthesis of hypericin". J. Struct. Biol. 169 (2): 161–171. doi:10.1016/j.jsb.2009.10.008. PMID   19853038.
  12. Murthy HN, Kim YS, Park SY, Paek KY (2014). "Hypericins: biotechnological production from cell and organ cultures". Appl. Microbiol. Biotechnol. 98 (22): 9187–9198. doi:10.1007/s00253-014-6119-3. PMID   25301586. S2CID   17487401.