Forskolin
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| Names | |
|---|---|
| IUPAC name
(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-6,10,10b-Trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-3-vinyldodecahydro-1H-benzo[f]chromen-5-yl acetate | |
| Identifiers | |
66428-89-5  | |
| 3D model (Jmol) | Interactive image |
| ChEBI | CHEBI:42471 |
| ChEMBL | ChEMBL52606 |
| ChemSpider | 43607 |
| DrugBank | DB02587 |
| ECHA InfoCard | 100.060.354 |
| 5190 | |
| PubChem | 47936 |
| UNII | 1F7A44V6OU |
| |
| |
| Properties | |
| C22H34O7 | |
| Molar mass | 410.51 g·mol−1 |
| Solubility | Soluble in organic solvents such as ethanol, chloroform and DMSO[1] |
| Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
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| Infobox references | |
Forskolin (coleonol) is a labdane diterpene that is produced by the Indian Coleus plant (Plectranthus barbatus). Forskolin is commonly used as a tool in biochemistry to raise levels of cyclic AMP (cAMP) in the study and research of cell physiology. Forskolin activates the enzyme adenylyl cyclase and increases intracellular levels of cAMP. cAMP is an important second messenger necessary for the proper biological response of cells to hormones and other extracellular signals. It is required for cell communication in the hypothalamus/pituitary gland axis and for the feedback control of hormones. Cyclic AMP acts by activating cAMP-sensitive pathways such as protein kinase A and Epac.
Biosynthesis
- As with other members of the large diterpene family of natural products, forskolin is derived from geranylgeranyl pyrophosphate (GGPP). Forskolin, however, contains some unique functional elements, key among them is the presence of a tetrahydropyran derived heterocyclic ring. This ring is synthesized after the formation of the trans-fused carbon ring systems are formed by a carbocation mediated cyclization. The remaining tertiary carbocation is quenched by a molecule of water. After deprotonation, the remaining hydroxyl group is free to form the heterocyclic ring. This cyclization can occur either by attack of the alcohol oxygen onto the allylic carbocation formed by loss of diphosphate, or by an analogous SN2' like displacement of the diphosphate.[2] This forms the core ring system A of forskolin.
- The remaining modifications of the core ring system A can putatively be understood as a series of oxidation reactions to form a poly-ol B which is then further oxidized and esterified to form the ketone and acetate ester moieties seen in forskolin. However, because the biosynthetic gene cluster has not been described, this putative synthesis could be incorrect in the sequence of oxidation/esterification events, which could occur in almost any order.
Safety
One study has shown that the lethal dose in rats (with the oral formulation) was >2,000 mg/kg.[3]
Safety in pregnancy
There is limited information on forskolin’s use in pregnant women. The safety has not yet been determined.[4] Forskolin should be used with caution or avoided altogether in women who are pregnant.[4]
References
- ↑ "Forskolin" (pdf). Sigma Aldrich.
- ↑ Dewick, P. M. (2009). Medicinal Natural Products (3rd ed.). Wiley. p. 232. ISBN 978-0470741689.
- ↑ Huerta M, Urzúa Z, Trujillo X, González-Sánchez R, Trujillo-Hernández B (2010). "Forskolin compared with beclomethasone for prevention of asthma attacks: a single-blind clinical trial". J Int Med Res. 38 (2): 661–668.
- 1 2 "Forskolin". Drugs.com. www.drugs.com.
Further reading
- Bubolz, A. H.; Li, H.; Wu, Q.; Liu, Y. (2005). "Enhanced oxidative stress impairs cAMP-mediated dilation by reducing Kv channel function in small coronary arteries of diabetic rats" (PDF). American Journal of Physiology. Heart and Circulatory Physiology. 289 (5): H1873–1880. doi:10.1152/ajpheart.00357.2005. PMID 15937095.
External links
- Scientific American: Sunless Suntan Proves Possible
- Research on suntanning effect of forskolin extract from Plectranthus barbatus