Forskolin

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Forskolin
Forskolin.svg
Names
Preferred IUPAC name
(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-Ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxododecahydro-1H-naphtho[2,1-b]pyran-5-yl acetate
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.060.354 Edit this at Wikidata
IUPHAR/BPS
UNII
  • InChI=1S/C22H34O7/c1-8-19(5)11-14(25)22(27)20(6)13(24)9-10-18(3,4)16(20)15(26)17(28-12(2)23)21(22,7)29-19/h8,13,15-17,24,26-27H,1,9-11H2,2-7H3/t13-,15-,16-,17-,19-,20-,21+,22-/m0/s1 checkY
    Key: OHCQJHSOBUTRHG-KGGHGJDLSA-N checkY
  • InChI=1/C22H34O7/c1-8-19(5)11-14(25)22(27)20(6)13(24)9-10-18(3,4)16(20)15(26)17(28-12(2)23)21(22,7)29-19/h8,13,15-17,24,26-27H,1,9-11H2,2-7H3/t13-,15-,16-,17-,19-,20-,21+,22-/m0/s1
    Key: OHCQJHSOBUTRHG-KGGHGJDLBB
  • CC(=O)O[C@H]1[C@H]([C@@H]2[C@]([C@H](CCC2(C)C)O)([C@@]3([C@@]1(O[C@@](CC3=O)(C)C=C)C)O)C)O
Properties
C22H34O7
Molar mass 410.507 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).
checkY  (what is checkY☒N ?)
Infobox references

Forskolin (coleonol) is a labdane diterpene that is produced by the Indian Coleus plant (Plectranthus barbatus). Other names include pashanabhedi, Indian coleus, makandi, HL-362, mao hou qiao rui hua.[2] As with other members of the large diterpene family of natural products, forskolin is derived from geranylgeranyl pyrophosphate (GGPP). Forskolin contains some unique functional elements, including the presence of a tetrahydropyran-derived heterocyclic ring. Forskolin is a commonly used material in laboratory research to increase levels of cyclic AMP by stimulation of adenylate cyclase.[2]

Mechanism of action[]

Forskolin is commonly used as a tool in biochemistry to raise levels of cyclic AMP (cAMP) in the study and research of cell physiology.[2][3] 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 via induction of corticotropin-releasing factor gene transcription.[4] Cyclic AMP acts by activating cAMP-sensitive pathways such as protein kinase A and EPAC1.

Chemistry[]

Derivatives[]

Its derivatives include colforsin daropate, ,[5] and ,[6] which may be more potent than forskolin at raising cAMP. These derivatives may have pharmaceutical utility against bronchoconstriction and heart failure.[7][8]

Biosynthesis[]

The heterocyclic ring is synthesized after the formation of the trans-fused carbon ring systems formed by a carbocation mediated cyclization. The remaining tertiary carbocation is quenched by a molecule of water. After deprotonation, the remaining hydroxy 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.[9] 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.

Other uses[]

Other than its utility for laboratory research, forskolin has been used in traditional medicine in the belief it affects various disorders, and has been proposed as a weight loss agent, but none of these uses are supported by sound clinical evidence.[2] Forskolin is widely used as supplement.

See also[]

References[]

  1. ^ "Forskolin" (PDF). Sigma Aldrich.
  2. ^ a b c d "Forskolin". Drugs.com. 2018. Retrieved 23 March 2018.
  3. ^ Alasbahi, RH; Melzig, MF (January 2012). "Forskolin and derivatives as tools for studying the role of cAMP". Die Pharmazie. 67 (1): 5–13. doi:10.1691/ph.2012.1642. PMID 22393824.
  4. ^ Kageyama, K; Tamasawa, N; Suda, T (July 2011). "Signal transduction in the hypothalamic corticotropin-releasing factor system and its clinical implications". Stress (Amsterdam, Netherlands). 14 (4): 357–67. doi:10.3109/10253890.2010.536279. PMID 21438777. S2CID 9631868.
  5. ^ Morinobu S, Fujimaki K, Okuyama N, Takahashi M, Duman RS (May 1999). "Stimulation of adenylyl cyclase and induction of brain-derived neurotrophic factor and TrkB mRNA by NKH477, a novel and potent forskolin derivative". Journal of Neurochemistry. 72 (5): 2198–205. doi:10.1046/j.1471-4159.1999.0722198.x. PMID 10217303.
  6. ^ Li Z, Wang J (November 2006). "A forskolin derivative, FSK88, induces apoptosis in human gastric cancer BGC823 cells through caspase activation involving regulation of Bcl-2 family gene expression, dissipation of mitochondrial membrane potential and cytochrome c release". Cell Biology International. 30 (11): 940–6. doi:10.1016/j.cellbi.2006.06.015. PMID 16889987. S2CID 7288869.
  7. ^ Wajima Z, Yoshikawa T, Ogura A, Imanaga K, Shiga T, Inoue T, Ogawa R (April 2002). "Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans". Critical Care Medicine. 30 (4): 820–6. doi:10.1097/00003246-200204000-00017. PMID 11940752. S2CID 22244620.
  8. ^ Sanbe A, Takeo S (July 1995). "Effects of NKH477, a water-soluble forskolin derivative, on cardiac function in rats with chronic heart failure after myocardial infarction". The Journal of Pharmacology and Experimental Therapeutics. 274 (1): 120–6. PMID 7616388.
  9. ^ Dewick, P. M. (2009). Medicinal Natural Products (3rd ed.). Wiley. p. 232. ISBN 978-0470741689.

External links[]

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