Secondary Metabolites from Eupenicillium parvum and Their in Vitro Binding Affinity for Human Opioid and Cannabinoid Receptors

León, Francisco; Gao, Jiangtao; Dale, Olivia R.; Wu, Yunshan; Habib, Eman S.; Husni, Afeef S.; Hill, Robert A.; Cutler, Stephen J.

doi:10.1055/s-0033-1351099

Cited by 21 publications

(18 citation statements)

References 22 publications

(29 reference statements)

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“…Compounds evaluated in the assay were run in competition experiments using both cannabinoid receptor subtypes, CB1 and CB2 [25,26]. Cannabinoid receptor binding assays were performed under the following conditions: 10 μM of each compound was incubated with 0.5 nM [ 3 H]-CP 55,940, a potent cannabinoid agonist with affinity to both receptor subtypes, and 10 μg CB1 or CB2 membrane [26] for 90 min in a 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

“…Cannabinoid receptor binding assays were performed under the following conditions: 10 μM of each compound was incubated with 0.5 nM [ 3 H]-CP 55,940, a potent cannabinoid agonist with affinity to both receptor subtypes, and 10 μg CB1 or CB2 membrane [26] for 90 min in a 96-well plate. The reaction was terminated via rapid vacuum filtration through GF/C filters presoaked with 0.3% BSA using a Perkin Elmer 96-well Unifilter (Perkin Elmer Life Sciences Inc., Boston, Mass.…”

Section: Methodsmentioning

confidence: 99%

“…All compounds evaluated in the assay were run in competition binding against the opioid receptor subtypes (δ, κ, μ), as well as the cannabinoid receptor subtypes mentioned above [26]. Saturation experiments were performed after each batch of membrane was scraped for each of the three opioid cell lines (δ, κ, μ) to determine the optimal tritium and membrane concentration to be used in the assay.…”

Section: Methodsmentioning

confidence: 99%

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Sulfated phenolic compounds from Limonium caspium: Isolation, structural elucidation, and biological evaluation

et al. 2015

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Three new compounds, (2S,3S)-5-methyldihydromyricetin (1), (2S,3S)-5-methyldihydromyricetin-3′-O-sulfate (2) and β-D-glucopyranoside, 3-methyl, but-3-en-1-yl 4-O-α-L-rhamnopyranosyl (3) have been isolated from the Limonium caspium, together with dihydromyricetin (4), dihydromyricetin-3′-O-sulfate (5), myricetin-3′-O-sulfate (6), 5-methylmyricetin (7), myricetin (8), myricetin-3-O-β-glucoside (9), as well as phloridzin (10), and tyramine (11). Compounds 5 and 6 were isolated for the first time as acids. This is the first report of all these compounds from this plant. Their structures were established by extensive NMR studies (1H NMR, 13C NMR, DEPT, 1H–1H COSY, HSQC, HMBC) as well as HRESIMS. All isolated compounds were evaluated for their antibacterial, antifungal, antimalarial and antileishmanial activities. Compounds 7, 8 and 9 exhibited good antifungal activity against Candida glabrata with IC50 values of 6.79, 15.37 and 8.53 μg/mL, respectively. Compound 8 displayed significant antimalarial activity against resistant and sensitive strains of Plasmodium falciparum with IC50 values of 1.82 and 1.51 μg/mL, respectively. Compounds 1, 4, 6, 8 and 9 showed excellent activity against Trypanosoma brucei with IC50 values of 6.93, 9.65, 8.52, 7.67 and 6.31 μg/mL, respectively. To date, this is the first report on the phytochemical and biological activity of secondary metabolites from L. caspium.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Sulfated phenolic compounds from Limonium caspium: Isolation, structural elucidation, and biological evaluation

et al. 2015

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“…Compounds 1 – 22 were evaluated in competition binding with cannabinoid receptor subtypes, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), as previously described (Thomas et al 2005; León et al 2013). Also, these compounds were tested against the opioid receptor subtypes ( δ , κ and μ ) as previously described (León et al 2013).…”

Section: Methodsmentioning

confidence: 99%

New ursane triterpenoids from Ficus pandurata and their binding affinity for human cannabinoid and opioid receptors

et al. 2016

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Phytochemical investigation of Ficus pandurata Hance (Moraceae) fruits has led to the isolation of two new triterpenoids, ficupanduratin A [1β-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (11) and ficupanduratin B [21α-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (17), along with 20 known compounds: α-amyrin acetate (1), α-amyrin (2), 3β-acetoxy-20-taraxasten-22-one (3), 3β-acetoxy-11α-methoxy-olean-12-ene (4), 3β-acetoxy-11α-methoxy-12-ursene (5), 11-oxo-α-amyrin acetate (6), 11-oxo-β-amyrin acetate (7), palmitic acid (8), stigmast-4,22-diene-3,6-dione (9), stigmast-4-ene-3,6-dione (10), stigmasterol (12), β-sitosterol (13), stigmast-22-ene-3,6-dione (14), stigmastane-3,6-dione (15), 3β,21β-dihydroxy-11α-methoxy-olean-12-ene (16), 3β-hydroxy-11α-methoxyurs-12-ene (18), 6-hydroxystigmast-4,22-diene-3-one (19), 6-hydroxystigmast-4-ene-3-one (20), 11α,21α-dihydroxy-3β-acetoxy-urs-12-ene (21), and β-sitosterol-3-O-β-D-glucopyranoside (22). Compound 21 is reported for the first time from a natural source. The structures of the 20 compounds were elucidated on the basis of IR, 1D (1H and 13C), 2D (1H–1H COSY, HSQC, HMBC and NOESY) NMR and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. In addition, their radioligand displacement affinity on opioid and cannabinoid receptors was assessed. Compounds 4, 11, and 15 exhibited good affinity towards the CB2 receptor, with displacement values of 69.7, 62.5 and 86.5 %, respectively. Furthermore, the binding mode of the active compounds in the active site of the CB2 cannabinoid receptors was investigated through molecular modelling.

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“…Cannabiniod and opioid competitive radioligand binding assays were performed as previously described (Giacometti et al, 2013; Husni et al, 2014; León et al 2013; Tarawneh et al, 2013). Membrane evaluations and saturation experiments were performed for all receptors to determine optimal receptor concentration (varied from 1 µg to 25 µg protein) and radioligand dissociation constant (K d ) for the membrane (varied between 0.5 nM to 5 nM).…”

Section: Methodsmentioning

confidence: 99%

In vitro opioid receptor affinity and in vivo behavioral studies of Nelumbo nucifera flower

Kumarihamy

León

Pettaway

et al. 2015

Journal of Ethnopharmacology

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Ethnopharmacological relevance Nelumbo nucifera Geartn., known as sacred lotus, has been used traditionally in South East Asia as a traditional medicine for various CNS disorders including stress, fever, depression, insomnia, and cognitive conditions. Aim of the study To investigate the in vitro cannabinoid and opioid receptor binding affinities, and in vivo behavioral actions of Nelumbo flower extracts and to isolate the potential compounds to treat CNS associated disorders. Materials and methods The white and pink flowers of N. nucifera were extracted with 95% EtOH, followed by acid-base partitioning using CHCl3 to give acidic and basic partitions. These partitions were subjected to Centrifugal Preparative TLC (CPTLC) to yield benzyltetrahydroisoquinoline (BTIQ) alkaloids and long chain fatty acids, identified by physical and spectroscopic methods. In addition, EtOH extracts and partitions were analyzed for chemical markers by UHPLC/MS and GC/MS. In vitro neuropharmacological effects were evaluated by cannabinoid (CB1 and CB2) and opioid [delta (δ), kappa (κ), and mu (μ)] competitive radioligand binding and GTPγS functional assays. The in vivo behavioral effect was studied through the use of the mouse tetrad assay at 10, 30, 75 and 100 mg/kg/ip doses that revealed the effect on locomotion, catalepsy, body temperature, and nociception of acidic and basic CHCl3 partitions, fractions, and compounds. Results Three aporphines, nuciferine (1), N-nor-nuciferine (2), asimilobine (3), and five BTIQs, armepavine (4), O-methylcoclaurine (5), N-methylcoclaurine (6), coclaurine (7), neferine (10), and a mixture of linoleic and palmitic acids (LA and PA), were identified and evaluated for cannabinoid and opioid receptor displacement activities. Compounds 5–7 showed binding affinities for the κ opioid receptor with equilibrium dissociation constant (Ki) values of 3.5±0.3, 0.9±0.1, 2.2±0.2 µM, respectively. Compound 10 displayed affinities for δ-and μ- opioid receptors with Ki values of 0.7±0.1 and 1.8±0.2 µM, respectively, and was determined to be a weak δ agonist by GTPγS functional assay. The mixture of LA and PA (1:1) showed an affinity for δ opioid receptor with a Ki value of 9.2±1.1 µM. The acidic and basic CHCl3 partitions, compounds 1 and 7, and 5–7 mixture were subjected to the tetrad assay, of which the acidic partition displayed decreased locomotion and increased catalepsy, antinociception, and hypothermia in animal at doses of 75–100 mg/kg/ip, and also showed clonic-tonic seizures upon touch at 100 mg/kg. Conclusion Bioassay-guided isolation revealed compounds 5–7, 10, and the mixture of LA and PA displayed various degrees of opioid receptor radioligand displacement affinities. The in vivo tetrad assay of acidic CHCl3 partition, enriched with aporphines 1 and 2, displayed actions on all four points of behavioral parameters. It can be concluded that the in vivo mild canabimimetic-type effect observed for the CHCl3 partition is likely mediated through other CNS mechanisms since the extracts, partitions, and...

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Secondary Metabolites from Eupenicillium parvum and Their in Vitro Binding Affinity for Human Opioid and Cannabinoid Receptors

Cited by 21 publications

References 22 publications

Sulfated phenolic compounds from Limonium caspium: Isolation, structural elucidation, and biological evaluation

Sulfated phenolic compounds from Limonium caspium: Isolation, structural elucidation, and biological evaluation

New ursane triterpenoids from Ficus pandurata and their binding affinity for human cannabinoid and opioid receptors

In vitro opioid receptor affinity and in vivo behavioral studies of Nelumbo nucifera flower

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