Leonurine

Leonurine (also known as "SCM-198" in research) is a pseudoalkaloid that has been isolated from Leonotis leonurus, Leonotis nepetifolia, Leonotis artemisia, Leonurus cardiaca (Motherwort), Leonurus sibiricus, as well as other plants of family Lamiaceae. Leonurine is easily extracted into water.[1]

Leonurine
Names
IUPAC name
4-(Diaminomethylideneamino)butyl 4-hydroxy-3,5-dimethoxybenzoate
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.208.686
KEGG
UNII
  • InChI=1S/C14H21N3O5/c1-20-10-7-9(8-11(21-2)12(10)18)13(19)22-6-4-3-5-17-14(15)16/h7-8,18H,3-6H2,1-2H3,(H4,15,16,17) Y
    Key: WNGSUWLDMZFYNZ-UHFFFAOYSA-N Y
  • InChI=1/C14H21N3O5/c1-20-10-7-9(8-11(21-2)12(10)18)13(19)22-6-4-3-5-17-14(15)16/h7-8,18H,3-6H2,1-2H3,(H4,15,16,17)
    Key: WNGSUWLDMZFYNZ-UHFFFAOYAI
  • O=C(OCCCC/N=C(\N)N)c1cc(OC)c(O)c(OC)c1
Properties
C14H21N3O5
Molar mass 311.338 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Pharmacology

Leonurine weakly binds to multiple GABA receptor sites including the GABA-A receptor.[2] [3] but shows much higher affinity as an 5-HT3A antagonist[4] 5-HT3A antagonists have been shown to help prevent nausea and vomiting as well as the negative effects of serotonin in the G.I tract.[5][6]

Leonurine can regulate a variety of functions including oxidative stress, inflammation, fibrosis, apoptosis, and metabolic disorder.[7][8][9]

Leonurine has demonstrated antidepressant like action and has been shown to increase levels of 5-hydroxytryptamine, noradrenaline, and dopamine in chronic mild stress studies on mice and inhibits the production of proinflammatory cytokines.[10][11][12]

Leonurine has been investigated as a potential treatment for cardiovascular disorders.[13][14][15][16] and protects against oxidative damage from ischemic stroke and demonstrates neuroprotective activity against focal cerebral ischemia brain injury induced on rats.[17][18][19]

Leonurine protects mice from pneumonia induced by influenza A[20]

Leonurine has demonstrated anti-cancer activity in vitro and in vivio.[21][22][23][24][25]

Metabolites

Metabolites of Leonurine in Rats dosed orally include Leonurine-10-O-sulfate (The sulfate conjugate of Leonurine), Leonurine-10-O-β-D-glucuronide (The glucuronide metabolite of Leonurine) and a O-demethylated Leonurine analog that has not yet had its structure definitively confirmed.[26]

Chemical synthesis

Leonurine can be synthesized starting from eudesmic acid. Reaction with sulfuric acid produces syringic acid. Protection with ethyl chloroformate followed by reaction with thionyl chloride SOCl2 and then tetrahydrofuran yields 4-carboethoxysyringic acid 4-chloro-1-butyl ester. The chloride is then converted to an amino group via a Gabriel synthesis (with potassium pthalimide) followed by hydrazinolysis (Ing–Manske procedure). The final step is reaction of the amine with S-methylisothiourea hemisulfate salt.

Leonurine synthesis[1]

See also

References
  1. "The Leonurine and its preparation". An Hui New Star Pharmaceutical Development Co. 2008. Archived from the original on 2008-05-15. Retrieved 2008-08-28.
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100244/
  3. https://www.researchgate.net/publication/273615504_GABAA_Receptor_Binding_Assays_of_Standardized_Leonurus_cardiaca_and_Leonurus_japonicus_Extracts_as_Well_as_Their_Isolated_Constituents
  4. https://www.frontiersin.org/articles/10.3389/fphar.2016.00219/full
  5. https://www.ncbi.nlm.nih.gov/books/NBK513318/
  6. https://www.drugs.com/drug-class/5ht3-receptor-antagonists.html#:~:text=5%2DHT3%20receptor%20antagonists%20(also,%2C%20radiation%20therapy%2C%20or%20postoperatively.
  7. https://link.springer.com/article/10.1007/s11655-019-3453-0
  8. https://academic.oup.com/rheumatology/article/56/8/1417/3739780?login=false
  9. https://www.spandidos-publications.com/10.3892/etm.2021.10633
  10. https://academic.oup.com/ijnp/article/20/11/886/4035667
  11. https://www.sciencedirect.com/science/article/abs/pii/S0197018610003396?via%3Dihub
  12. https://www.frontiersin.org/articles/10.3389/fphar.2021.742954/full
  13. https://onlinelibrary.wiley.com/doi/10.1002/brb3.1995
  14. hhttps://journals.lww.com/cardiovascularpharm/Abstract/2021/02000/Leonurine_Attenuates_Myocardial_Fibrosis_Through.10.aspx
  15. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/bmc.1699
  16. https://pubmed.ncbi.nlm.nih.gov/23127783/
  17. https://onlinelibrary.wiley.com/doi/10.1111/cns.13146/
  18. https://pubs.acs.org/doi/10.1021/acschemneuro.1c00200
  19. https://pubmed.ncbi.nlm.nih.gov/22842526/
  20. https://academic.oup.com/femspd/article-abstract/79/7/ftab045/6372906?redirectedFrom=fulltext&login=false
  21. http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7377&category_id=173&option=com_virtuemart&vmcchk=1&Itemid=1
  22. https://www.frontiersin.org/articles/10.3389/fphar.2021.657724/full
  23. https://www.tandfonline.com/doi/full/10.3109/13880209.2014.1001406
  24. https://www.dovepress.com/leonurine-promotes-cisplatin-sensitivity-in-human-cervical-cancer-cell-peer-reviewed-fulltext-article-DDDT
  25. https://www.eurekaselect.com/article/111531
  26. https://www.hindawi.com/journals/tswj/2014/947946/

Further reading
  • Cheng KF, Yip CS, Yeung HW, Kong YC (May 1979). "Leonurine, an improved synthesis". Experientia. 35 (5): 571–2. doi:10.1007/BF01960323. PMID 446644. S2CID 22601565.
  • Huang, L., Xu, D. Q., Chen, Y. Y., Yue, S. J., & Tang, Y. P. (2021). Leonurine, a potential drug for the treatment of cardiovascular system and central nervous system diseases. Brain and behavior, 11(2), e01995. PMID 33300684 PMC 7882174 doi:10.1002/brb3.1995
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