Guineesine

Guineesine

Names
IUPAC name (2E,4E,12E)-13-(1,3-Benzodioxol-5-yl)-N-(2-methylpropyl)trideca-2,4,12-trienamide
Other names Guineensine
Identifiers
CAS Number	55038-30-7
3D model (Jmol)	Interactive image
ChEMBL	ChEMBL404184
PubChem	6442405
InChI InChI=1S/C24H33NO3/c1-20(2)18-25-24(26)14-12-10-8-6-4-3-5-7-9-11-13-21-15-16-22-23(17-21)28-19-27-22/h8,10-17,20H,3-7,9,18-19H2,1-2H3,(H,25,26)/b10-8+,13-11+,14-12+ Key: FPMPOFBEYSSYDQ-AUVZEZIHSA-N=
SMILES CC(C)CNC(=O)/C=C/C=C/CCCCCC/C=C/C1=CC2=C(C=C1)OCO2
Properties
Chemical formula	C24H33NO3
Molar mass	383.53 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Guineesine (or guineensine) is an alkaloid isolated from long pepper (Piper longum)^[1] and black pepper (Piper nigrum).^[2]

Biological activities

Reuptake inhibition

Guineenine seems to potently inhibit the cellular reuptake of anandamide and 2-arachidonoylglycerol (EC₅₀ = 290 nM).^[3][4] This causes an increase in the activity of the two neurotransmitters which are classified as endogenous cannabinoids.

Cannabimimetic effects

Guineesine can dose-dependently produce cannabimimetic effects^[5] which are indicated by potent catatonic, analgesic, hypo-locomotive and hypo-thermic effects. In addition, the analgesic and catatonic effects were reversed by the cannabinoid receptor type 1 (CB1) antagonist rimonabant.^[4]

Enzyme activities

Guineesine also appears to possess significant monoamine oxidase inhibitory (MAOI) effects (IC₅₀ = 139.2 μM).^[6]

References

1. Liu W, Jiang Z, Chen J, Zhang X, Ma Y (May 2009). "荜茇三氯甲烷部位化学成分研究" [Chemical constituents from air-dried Piper longum]. Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica (in Chinese). 34 (9): 1101–3. PMID 19685743.
2. Park IK (2011). "Insecticidal activity of isobutylamides derived from Piper nigrum against adult of two mosquito species, Culex pipiens pallens and Aedes aegypti". Natural Product Research. 26 (22): 2129–31. doi:10.1080/14786419.2011.628178. PMID 22010905.
3. Sharma C, Sadek B, Goyal SN, Sinha S, Kamal MA, Ojha S (2015). "Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development". Evidence-Based Complementary and Alternative Medicine. 2015: 238482. doi:10.1155/2015/238482. PMID 26664449.
4. Nicolussi S, Viveros-Paredes JM, Gachet MS, Rau M, Flores-Soto ME, Blunder M, Gertsch J (February 2014). "Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice". Pharmacological Research. 80: 52–65. doi:10.1016/j.phrs.2013.12.010. PMID 24412246.
5. Nicolussi S, Chicca A, Rau M, Rihs S, Soeberdt M, Abels C, Gertsch J (December 2014). "Correlating FAAH and anandamide cellular uptake inhibition using N-alkylcarbamate inhibitors: from ultrapotent to hyperpotent". Biochemical Pharmacology. 92 (4): 669–89. doi:10.1016/j.bcp.2014.09.020. PMID 25283614.
6. Lee SA, Hwang JS, Han XH, Lee C, Lee MH, Choe SG, Hong SS, Lee D, Lee MK, Hwang BY (June 2008). "Methylpiperate derivatives from Piper longum and their inhibition of monoamine oxidase". Archives of Pharmacal Research. 31 (6): 679–83. doi:10.1007/s12272-001-1212-7. PMID 18563347.