Evidence-Based Complementary and Alternative Medicine

Review Article

Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development

Table 1

The physicochemical properties and common and IUPAC name of lead compounds modulating cannabinoid receptors.
Molecule & IUPAC nameChemical propertiesCommon name(s)
Amyrin
(3S,4aR,6aR,6bS,8aR,12aR,14aR,14bR)-4,4,6a,6b,8a,11,11,14b-Octamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-ol		M. Wt.: 426.71 [g/mol]
M. formula: C30H50O
XLogP3-AA: 9.2
H-bond donor/acceptor: 1/1		Olean-12-en-3-beta-ol
Auroglaucin
2-[(1E,3E,5E)-Hepta-1,3,5-trienyl]-3,6-dihydroxy-5-(3-methylbut-2-enyl)benzaldehyde		M. Wt.: 298.37618 [g/mol]
M. formula: C19H22O3 
XLogP3-AA: 5.4
H-bond donor/acceptor: 2/3		Auroglaucine
Biochanin A
5,7-Dihydroxy-3-(4-methoxyphenyl)chromen-4-one		M. Wt.: 284.26 [g/mol]
M. formula: C16H12O5 
XLogP3-AA: 3
H-bond donor/acceptor: 2/5		5,7-Dihydroxy-4′-methoxyisoflavone
Betulinic acid
(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-Hydroxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexa-decahydrocyclopenta[a]chrysene-3a-carboxylic acid		M. Wt.: 456.70 [g/mol]
M. formula: C30H48O3 
XLogP3-AA: 8.2
H-bond donor/acceptor: 2/3		3β-Hydroxy-20(29)-lupaene-28-oic acid
Celastrol
(2R,4aS,6aR,6aS,14aS,14bR)-10-Hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid		M. Wt.: 450.60962 [g/mol]
M. formula: C29H38O4
XLogP3: 5.9
H-bond donor/acceptor: 2/4		Celastrol; tripterine; tripterin; celastrol, Celastrus scandens
Beta-caryophyllene
(1R,4E,9S)-4,11,11-Trimethyl-8-methylidenebicyclo[7.2.0]undec-4-ene		M. Wt.: 204.35 [g/mol]
M. formula: C15H24 
XLogP3-AA: 4.4
H-bond donor/acceptor: 0/0		(−)-trans-Caryophyllene
Chelerythrine
1,2-Dimethoxy-12-methyl-1,3]benzodioxolo[5,6-c]phenanthridin-12-ium		M. Wt.: 348.37 [g/mol]
M. formula: C21H18N 
XLogP3-AA: 4.6
H-bond donor/acceptor: 0/4		1,2-Dimethoxy-12-methyl(1,3)benzodioxolo(5,6-c)phenanthridinium
Curcumin
(1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione		M. Wt.: 368.37 [g/mol]
M. formula: C21H20O6 
XLogP3-AA: 3.2
H-bond donor/acceptor: 2/6		Diferuloylmethane
Cyanidin
2-(3,4-Dihydroxyphenyl)chromenylium-3,5,7-triol		M. Wt.: 287.24 [g/mol]
M. formula: C15H11  
H-bond donor/acceptor: 5/5		Cyanidol, 3,5,7,3′,4′-pentahydroxyflavylium
Cyanidin-3,5-di-O-glucoside
(2S,3R,4S,5S,6R)-2-[2-(3,4-Dihydroxyphenyl)-7-hydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromenylium-5-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol		M. Wt.: 611.52 [g/mol]
M. formula: C27H31  
H-bond donor/acceptor: 11/15		Cyanin,
cyanidin 3,5-O-diglucoside
Cyanidin-3-O-glucoside
2-(3,4-Dihydroxyphenyl)-5-hydroxy-3-[(3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-7-one		M. Wt.: 448.37 [g/mol]
M. formula: C21H20O11 
XLogP3-AA: −1.2
H-bond donor/acceptor: 7/11		—
Cyanidin 3-galactoside
(2S,5R)-2-[2-(3,4-Dihydroxyphenyl)-5,7-dihydroxychro-menylium-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol		M. Wt.: 449.38 [g/mol]
M. formula: C21H21  
H-bond donor/acceptor: 8/10		Idaein, cyanidin 3-O-galactoside
Cyanidin 3-O-rutinoside
2-[[6-[2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-chromenylium-3-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methoxy]-6-methyloxane-3,4,5-triol chloride		M. Wt.: 630.97 [g/mol]
M. formula: C27H31ClO15 
H-bond donor/acceptor: 10/15		Meralop, 3-O-rutino sylcyanidin,7,4′-dihydroxyflavilium chloride
Delphinidin
2-(3,4,5-Trihydroxyphenyl)chromenylium-3,5,7-triol		M. Wt.: 303.24 [g/mol]
M. formula: C15H11  
H-bond donor/acceptor: 6/6		3,3′,4′,5,5′,7-Hexahydroxyflavylium
Euphol
(3S,5R,10S,13S,14S,17S)-4,4,10,13,14-Pentamethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,5,6,7,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-ol		M. Wt.: 426.71 [g/mol]
M. formula: C30H50O
XLogP3-AA: 8.9
H-bond donor/acceptor: 1/1		Eupha-8,24-dienol
18β-Glycyrrhetinic acid
(2S,4aS,6aR,6aS,6bR,10S,12aS,14bR)-10-Hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid		M. Wt.: 470.68 [g/mol]
M. formula: C30H46O4 
XLogP3-AA: 6.4
H-bond donor/acceptor: 2/4		18β-Glycyrrhetic acid, glycyrrhetinic acid
Grenadamide
(5E)-N-[(E)-10-Chloro-4,6-dimethyl-5-oxodec-9-en-2-yl]-5-(chloromethylidene)octanamide		M. Wt.: 404.4141 [g/mol]
M. formula: C21H35Cl2NO2 
XLogP3-AA: 6.1
H-bond donor/acceptor: 1/2		—
Guineensine
(2E,4E,12E)-13-(1,3-Benzodioxol-5-yl)-N-(2-methylpropyl)trideca-2,4,12-trienamide		M. Wt.: 383.52 [g/mol]
M. formula: C24H33NO3 
XLogP3-AA: 6.8
H-bond donor/acceptor: 1/3		Pipyahyine
Leucettamol A
(2S,3R,5Z,8Z,11Z,14Z,17Z,20Z,28R,29S)-2,29-Diaminotriaconta-5,8,11,14,17,20-hexaene-3,28-diol 		M. Wt.: 472.74 [g/mol]
M. formula: C30H52N2O2 
XLogP3-AA: 6.2
H-bond donor/acceptor: 4/4		—
Magnolol
2-(2-Hydroxy-5-prop-2-enylphenyl)-4-prop-2-enylphenol		M. Wt.: 266.33 [g/mol]
M. formula: C18H18O2 
XLogP3-AA: 5
H-bond donor/acceptor: 2/2		5,5′-Diallyl-2,2′-dihydroxybiphenyl
Methylhonokiol
2-(4-Methoxy-3-prop-2-enylphenyl)-4-prop-2-enylphenol		M. Wt.: 280.36 [g/mol]
M. formula: C19H20O2 
XLogP3-AA: 5.3
H-bond donor/acceptor: 1/2		4′-Methoxy-3′,5-di-2-propenyl-(1,1′-biphenyl)-2-ol,4-methoxyhonokiol
Pristimerin
Methyl (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylate		M. Wt.: 464.63 [g/mol]
M. formula: C30H40O4 
XLogP3-AA: 6.3
H-bond donor/acceptor: 1/4		24-Nor-D:A-friedooleana-1(10),3,5,7-tetraen-29-oic acid
Quercetin
2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one		M. Wt.: 302.23 [g/mol]
M. formula: C15H10O7 
XLogP3: 1.5
H-bond donor/acceptor: 5/7		—
Resveratrol
5-[(E)-2-(4-Hydroxyphenyl)ethenyl]benzene-1,3-diol		M. Wt.: 228.24 [g/mol]
M. formula: C14H12O3 
XLogP3-AA: 3.1
H-bond donor/acceptor: 3/3		3,4′,5-Trihydroxystilbene
Rutamarin
2-[6-(2-Methylbut-3-en-2-yl)-7-oxo-2,3-dihydrofuro[3,2-g]chromen-2-yl]propan-2-yl acetate		M. Wt.: 356.41 [g/mol]
M. formula: C21H24O5 
XLogP3-AA: 4.4
H-bond donor/acceptor: 0/5		—
Salvinorin A
Methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate		M. Wt.: 432.46 [g/mol]
M. formula: C23H28O8 
XLogP3-AA: 2.5
H-bond donor/acceptor: 0/8		Divinorin A
SanguinarineM. Wt.: 332.32 [g/mol]
M. formula: C20H14N  
XLogP3-AA: 4.4
H-bond donor/acceptor: 0/4		Dimethylene dioxybenzphenanthridine
γ-Sanshool
(2E,4E,8Z,10E,12E)-N-Propan-2-yltetradeca-2,4,8,10,12-pentaenamide		M. Wt.: 259.38 [g/mol]
M. formula: C17H25NO
XLogP3-AA: 4.3
H-bond donor/acceptor: 1/1		—
Miconioside B
(2S)-7-[(2S,4S,5S)-6-[[(2R,3S)-3,4-Dihydroxy-4-(hydroxylmethyl)oxolan-2-yl]oxymethyl]-3,4,5-tri-hydroxyoxan-2-yl]oxy-5-hydroxy-2-(4-hydroxy-phenyl)-6,8-dimethyl-2,3-dihydrochromen-4-one		M. Wt.: 594.56 [g/mol]
M. formula: C28H34O14 
XLogP3-AA: −0.5
H-bond donor/acceptor: 8/14		Farrerol 7-O-beta-D-apiofuranosyl(1->6)-beta-D-glucopyranoside
Piperine
(2E,4E)-5-(1,3-Benzodioxol-5-yl)-1-piperidin-1-ylpenta-2,4-dien-1-one		M. Wt.: 285.33 [g/mol]
M. formula: C17H19NO3 
XLogP3: 3.5
H-bond donor/acceptor: 0/3		1-Piperoylpiperidine
Malvidin
2-(4-Hydroxy-3,5-dimethoxyphenyl)chromenylium-3,5,7-triol		M. Wt.: 331.29 [g/mol]
M. formula: C17H15  
H-bond donor/acceptor: 4/6		3′,5′-Dimethoxy-3,4′,5,7-tetrahydroxy flavylium acid anion
Matteucinol
5,7-Dihydroxy-2-(4-methoxyphenyl)-6,8-dimethyl-2,3-dihydrochromen-4-one		M. Wt.: 314.33 [g/mol]
M. formula: C18H18O5 
XLogP3-AA: 3.4
H-bond donor/acceptor: 2/5		(2S)-5,7-Dihydroxy-2-(4-methoxyphenyl)-6,8-dimethyl-2,3-dihydro-4H-chromen-4-one
Monocillin II
(4E,8E,11S)-15-Hydroxy-11-methyl-12-oxabicyclo[12.4.0]octadeca-1(14),4,8,15,17-pentaene-3,13-dione		M. Wt.: 300.349 [g/mol]
M. formula: C18H20O4 
XLogP3-AA: 4.1
H-bond donor/acceptor: 1/4		—
Nonivamide
N-[(4-Hydroxy-3-methoxyphenyl)methyl]nonanamide		M. Wt.: 293.40 [g/mol]
M. formula: C17H27NO3 
XLogP3-AA: 4.2
H-bond donor/acceptor: 2/3		N-Vanillyl pelargonamide, pelargonic acid vanillylamide
Peonidin
2-(4-Hydroxy-3-methoxyphenyl)chromenylium-3,5,7-triol		M. Wt.: 301.27 [g/mol]
M. formula: C16H13  
H-bond donor/acceptor: 4/5		3,4′,5,7-Tetrahydroxy-3′-methoxyflavylium
Pelargonidin
2-(4-Hydroxyphenyl)chromenylium-3,5,7-triol		M. Wt.: 271.24 [g/mol]
M. formula: C15H11  
H-bond donor/acceptor: 4/4		3,4′,5,7-Tetrahydroxy flavylium chloride
RadicicolM. Wt.: 364.77698 [g/mol]
M. formula: C18H17ClO6 
XLogP3-AA: 3.4
H-bond donor/acceptor: 2/6		Monorderne, radisico, melanotetan II, monorden A
Sciadonic acid
(5E,11E,14E)-Icosa-5,11,14-trienoic acid		M. Wt: 306.48 [g/mol]
M. formula: C20H34O2 
XLogP3-AA: 6.7
H-bond donor: 1/2		Icosa-5,11,14-trienoic acid, 5c,11c,14c-eicosatrienoic acid
Semiplenamides A
(2E,6E)-N-(2-Hydroxyethyl)-2-methylicosa-2,6-dienamide		M. Wt.: 365.59 [g/mol]
M. formula: C23H43NO2 
XLogP3-AA: 7.7
H-bond donor/acceptor: 2/2		—
Semiplenamides B
2-[[(2E,6E)-2-Methylicosa-2,6-dienoyl]amino]ethyl acetate		M. Wt.: 407.62 [g/mol]
M. formula: C25H45NO3 
XLogP3-AA: 8.3
H-bond donor/acceptor: 1/3		—
Semiplenamides G
2-[[(2S,3R)-2-Methyl-3-pentadecyloxirane-2-carbonyl]amino] propyl acetate		M. Wt.: 411.61 [g/mol]
M. formula: C24H45NO4 
XLogP3-AA: 7.6
H-bond donor/acceptor: 1/4		—
Serinolamide A
(E)-N-[(2R)-1-Hydroxy-3-methoxypropan-2-yl]-N-methyloctadec-4-enamide		M. Wt.: 383.6083 [g/mol]
M. formula: C23H45NO3 
XLogP3-AA: 6.6
H-bond donor/acceptor: 1/3		(4E)-N-[(2R)-1-Hydroxy-3-methoxy-2-propanyl]-N-methyl-4-octadecenamide
VoacamineM. Wt.: 704.89 [g/mol]
M. formula: C43H52N4O5 
XLogP3-AA: 6.1
H-bond donor/acceptor: 2/7		Voacanginine, voacamine
Yangonin
4-Methoxy-6-[(E)-2-(4-methoxyphenyl)ethenyl]pyran-2-one		M. Wt.: 258.26 [g/mol]
M. formula: C15H14O4 
XLogP3-AA: 2.7
H-bond donor/acceptor: 0/4		4-Methoxy-6-(β-(p-anisyl)vinyl)-α-pyrone
The XLogP3-AA data, molecular weight, molecular formula, and H-bond donor/H-bond were collected from NCBI, http://www.ncbi.nlm.nih.gov/pccompound/?term.