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1.
Fitoterapia ; 145: 104610, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32433929

ABSTRACT

Persicaria maculosa (Polygonaceae) has been used as edible and as medicinal plant since ancient times. As a result of multistep chromatographic purifications, chalcones [2'-hydroxy-3',4',6'-trimethoxychalcone (1), pashanone (2), pinostrobin chalcone (3)], flavanones [6-hydroxy-5,7-dimethoxyflavanone (4), pinostrobin (5), onysilin (6), 5-hydroxy-7,8-dimethoxyflavanone (7)], flavonol [3-O-methylgalangin (8)], stilbene [persilben (9)], diarylheptanoids [1,7-diphenylhept-4-en-3-one (10), dihydroyashabushiketol (12), yashabushidiol B (13)] and 3-oxo-α-ionol-glucoside (11) were isolated from P. maculosa. The present paper reports for the first time the occurrence of diarylheptanoid-type constituents in the family Polygonaceae. Cytotoxicity of 1-5, 7 and 9-11 on 4 T1 mouse triple negative breast cancer cells was assayed by MTT test. None of the tested compounds reduced the cell viability to less than 80% of the control. On non-tumorigenic D3 human brain endothelial cells the decrease of cell viability was observed in case of 1 and 2. Further impedance measurements on 4 T1 and D3 cells a concentration-dependent decrease in the cell index of both cell types was demonstrated for 1, while 2 proved to be toxic only on endothelial cells.


Subject(s)
Diarylheptanoids/pharmacology , Flavonoids/pharmacology , Phytochemicals/pharmacology , Polygonaceae/chemistry , Stilbenes/pharmacology , Animals , Brain/cytology , Cell Line, Tumor , Diarylheptanoids/isolation & purification , Endothelial Cells/drug effects , Flavonoids/isolation & purification , Humans , Hungary , Mice , Molecular Structure , Phytochemicals/isolation & purification , Plants, Medicinal/chemistry , Stilbenes/isolation & purification , Toxicity Tests
2.
Pak J Pharm Sci ; 33(4): 1593-1597, 2020 Jul.
Article in English | MEDLINE | ID: mdl-33583792

ABSTRACT

Phytochemical investigation of the whole plant of Filago vulgaris Lam. (Asteraceae) resulted in the isolation and characterization of seven compounds, including a rare methoxylated flavonol (araneol), tetrahydrofurofuranolignans (pinoresinol and syringaresinol), p-hydroxybenzaldehyde, vanillin, vanillic acid and scopoletin. The structures of the compounds were determined by NMR and mass spectroscopy. All compounds were first obtained from this species and reported for the genus Filago. Our results demonstrate that highly methoxylated flavonols lacking substituents on ring B and lignans can be regarded as taxonomic markers for the tribe Inuleae. The lipophilic extract of F. vulgaris was found to have antiproliferative activity against HeLa cells (62.1±0.9% inhibition at 30 µ/ml), and araneol was highly effective against this tumour cell line (IC50 8.36 µ M).


Subject(s)
Asteraceae/chemistry , Cell Proliferation/drug effects , Flavonoids/chemistry , Flavonoids/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Cell Line, Tumor , Flavonols/chemistry , Flavonols/pharmacology , Furans/chemistry , Furans/pharmacology , HeLa Cells , Humans , Lignans/chemistry , Lignans/pharmacology , MCF-7 Cells
3.
Fitoterapia ; 122: 90-94, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28864041

ABSTRACT

The present study aimed at the phytochemical and pharmacological investigation of Sideritis montana L. (Lamiaceae). Two new abietane diterpenes [sideritins A (1) and B (2)] were isolated from the methanol extract of the plant. Six known compounds [pomiferin E (3), 9α,13α-epi-dioxyabiet-8(14)-en-18-ol (4), paulownin (5), 6-methoxysakuranetin (6), 3-oxo-α-ionol (7) and 4-allyl-2,6-dimethoxyphenol glucoside (8)] were also obtained from the plant. The structures were determined by means of HREIMS and NMR experiments. The antiproliferative effect of the isolated compounds was investigated on human cancer cell lines (HeLa, SiHa and C33A) at 10 and 30µM concentrations, using the MTT assay. The results demonstrated that pomiferin E (3) and 6-methoxysakuranetin (6) displayed considerable activity [inhibition (%)±SEM: 46.93±2.35 on HeLa (pomiferin E), and 51.52±2.45 on C33A (6-methoxysakuranetin)] at 30µM concentration.


Subject(s)
Abietanes/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Sideritis/chemistry , Abietanes/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Molecular Structure
4.
Phytomedicine ; 34: 44-49, 2017 Oct 15.
Article in English | MEDLINE | ID: mdl-28899508

ABSTRACT

BACKGROUND: Transient Receptor Potential Vanilloid 1 (TRPV1) confers noxious heat and inflammatory pain signals in the peripheral nervous system. Clinical trial of resiniferatoxin from Euphorbia species is successfully aimed at TRPV1 in cancer pain management and heading toward new selective painkiller status that further validates this target for drug discovery efforts. Evodia species, used in traditional medicine for hundreds of years, are a recognised source of different TRPV1 agonists, but no antagonist has yet been reported. HYPOTHESIS/PURPOSE: In a search for painkiller leads, we noted for the first time a TRPV1 antagonist activity in the fresh fruits of Tetradium daniellii (Benn.) T.G. Hartley (syn. Evodia hupehensis Dode). METHODS: Through a combination of extraction and purification methods with functional TRPV1-specific Ca2+ uptake assays (bioactivity-guided fractionation/isolation/purification); we isolated a new painkiller candidate that is a distant structural homologue of capsiate exovanilloids and endovanilloids such as anandamide, but a putative competitive inhibitor of the TRPV1. Four additional inactive compounds (N-isobutyl-4,5-epoxy-2E-decadienamide, geranylpsoralen, 8-(7',8'-epoxygeranyloxy)psoralen, and xanthotoxol) were also co-purified with pellitorine. Their structures were established by extensive 1D- and 2D-NMR spectroscopic analysis. RESULTS: 1H- and 13C NMR determination of the chemical structure revealed it to be pellitorine, (2E,4E)-N-(2-methylpropyl)deca-2,4-dienamide, which can compete structurally with algesics released in inflammation. In contrast to previous isolates from Evodia species, pellitorine blocked capsaicin-evoked Ca2+ uptake with an IC50 of 154 µg/ml (0.69 mM/l). N-Isobutyl-4,5-epoxy-2E-decadienamide and geranylpsoralen, 8-(7',8'-epoxygeranyloxy)psoralen, and xanthotoxol did not affect the TRPV1. CONCLUSION: This is the first evidence that pellitorine, an aliphatic alkylamide analogue of capsaicin, can serve as an antagonist of the TRPV1 and may inhibit exovanilloid-induced pain.


Subject(s)
Analgesics/pharmacology , Fatty Acids, Unsaturated/pharmacology , Plant Extracts/pharmacology , Polyunsaturated Alkamides/pharmacology , Rutaceae/chemistry , TRPV Cation Channels/antagonists & inhibitors , Animals , Cell Line , Evodia/chemistry , Fatty Acids, Unsaturated/chemistry , Fruit/chemistry , Humans , Mice, Inbred BALB C , Polyunsaturated Alkamides/chemistry
5.
Acta Biol Hung ; 68(3): 300-309, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28901802

ABSTRACT

Physalin D was isolated from the methanol extract of Physalis alkekengi L. fruits by combination of different chromatographic methods (CPC, TLC, HPLC). The structure was elucidated based on 1H and 13C NMR spectral analysis with the aid of 2D-correlation spectroscopy (1H, 1H-COSY, HSQC and HMBC) and comparison with literature data. The quantity of physalin D in mature and immature fruits and calyces was determined by RP-HPLC-UV method. Among the studied samples, immature calyx showed the highest content of physalin D (0.7880 ± 0.0612%), while mature calyx contained 4 times less amount (0.2028 ± 0.016%). The physalin D content of the fruit was much lower; immature fruits contained 0.0992 ± 0.0083% physalin D and mature fruits 0.0259 ± 0.0021%. The antiproliferative activity of the CHCl3 extract and its fractions was tested on three cancer cell lines (HeLa, MCF-7 and A431). The antiproliferative activity of physalin D is discussed with regard the published data.


Subject(s)
Flowers/chemistry , Fruit/chemistry , Neoplasms, Experimental/drug therapy , Physalis/chemistry , Secosteroids/administration & dosage , Secosteroids/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Dose-Response Relationship, Drug , HeLa Cells , Humans , MCF-7 Cells , Neoplasms, Experimental/pathology , Plant Extracts/administration & dosage , Plant Extracts/chemistry
6.
Acta Biol Hung ; 68(2): 232-236, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28605979

ABSTRACT

In the course of our pharmacological screening of Polygonaceae species occurring in the Carpathian Basin the extracts prepared from the roots of Rumex thyrsiflorus showed promising antiproliferative, xanthine oxidase inhibitory and antibacterial activities. The present work deals with the isolation of compounds from the root of the plant. After multistep separation process, four compounds were obtained from the n-hexane, chloroform and ethyl acetate soluble fractions of the methanol extract of the root. The structures of the isolated compounds were determined as 1-palmitoylglycerol, ß-sitosterol, (-)-epicatechin, and procyanidin B5.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Enzyme Inhibitors/pharmacology , Plant Extracts/pharmacology , Plant Roots/chemistry , Rumex/chemistry , Xanthine Oxidase/antagonists & inhibitors , Anti-Bacterial Agents/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Enzyme Inhibitors/chemistry , Humans , Plant Extracts/chemistry
7.
PLoS One ; 12(3): e0174170, 2017.
Article in English | MEDLINE | ID: mdl-28328973

ABSTRACT

Salinity-induced osmotic, ionic and oxidative stress responses were investigated on Asakaze/Manas wheat/barley addition lines 7H, 7HL and 7HS, together with their barley (salt-tolerant) and wheat (relatively salt-sensitive) parents. Growth, photosynthetic activity, chlorophyll degradation, proline, glycine betaine accumulation, sugar metabolism, Na+ and K+ uptake and transport processes and the role of polyamines and antioxidants were studied in young plants grown in hydroponic culture with or without salt treatment. Changes in plant growth and photosynthetic activity of plants demonstrated that the salt tolerance of the addition lines 7H and 7HL was similar to that of barley parent cv. Manas, while the sensitivity of the addition line 7HS was similar to that of the wheat parent cv. Asakaze. The Na accumulation in the roots and shoots did not differ between the addition lines and wheat parent. The activation of various genes related to Na uptake and transport was not correlated with the salt tolerance of the genotypes. These results indicated that the direct regulation of Na transport processes is not the main reason for the salt tolerance of these genotypes. Salt treatment induced a complex metabolic rearrangement in both the roots and shoots of all the genotypes. Elevated proline accumulation in the roots and enhanced sugar metabolism in the shoots were found to be important for salt tolerance in the 7H and 7HL addition lines and in barley cv. Manas. In wheat cv. Asakaze and the 7HS addition line the polyamine metabolism was activated. It seems that osmotic adjustment is a more important process in the improvement of salt tolerance in 7H addition lines than the direct regulation of Na transport processes or antioxidant defence.


Subject(s)
Chromosomes, Plant/genetics , Hordeum/genetics , Salt Tolerance/genetics , Sodium Chloride/metabolism , Stress, Physiological/genetics , Triticum/genetics , Genes, Plant/genetics , Hordeum/metabolism , Osmosis/physiology , Photosynthesis/genetics , Plant Roots/genetics , Plant Roots/metabolism , Plant Shoots/genetics , Plant Shoots/metabolism , Potassium/metabolism , Salinity , Sodium/metabolism , Triticum/metabolism
8.
Med Chem ; 13(5): 498-502, 2017.
Article in English | MEDLINE | ID: mdl-27991400

ABSTRACT

BACKGROUND: Centaurea virgata Lam. is a species widely used in the traditional medicine in Turkey for the treatment of diabetes, allergy and gastric ulcers. The rationale of its use in the therapy has not been studied previously, therefore the present work aimed at the chemicalpharmacological evaluation of the plant. OBJECTIVE: The xanthine oxidase (XO) inhibitory activity of the MeOH extract and its subextracts (n-hexane, CHCl3 and remaining MeOH-H2O) prepared from C. virgata was investigated in vitro. Moderate activity was exerted in case of the CHCl3 extract (98.9 ± 15.8 µg/mL), therefore constituents of this extract were analysed. METHOD: Different purification steps, such as VLC, CPC, PLC and crystallization were used for the isolation, and ESIMS, NMR, LC-MS and authentic standards were applied for identification of the compounds. XO inhibitory and DPPH assays were used for evaluation of the bioactivities. RESULTS: Sesquiterpenes [8α-hydroxysonchucarpolide, 8α-(3,4-dihydroxy-2-methylenebutanoyloxy)- dehydromelitensine, and cnicin], flavones (apigenin, hispidulin, salvigenin, eupatorin, 3'-methyleupatorin), and the flavonol isokaempferide were isolated from the active extract. The XO-inhibitory activity of these compounds was analyzed using allopurinol as a positive control (IC50 7.49 ± 0.29 µM). It was found that sesquiterpenes and flavonoids, containing 7- OMe group, are inactive. CONCLUSION: 7-Hydroxyflavones (apigenin and hispidulin) exerted significant XO inhibitory effect with IC50 values of 0.99 ± 0.33 µM and 4.88 ± 1.21 µM, respectively. Therefore, these compounds are responsible for the XO-inhibitory effect of the extract. The free radical scavenging activity of the isolated flavonoids was determined by DPPH assay, and it was stated that none of the compounds have substantial antioxidant activity, therefore the reduced generation of reactive oxygen species may be the consequence only of XO inhibition.


Subject(s)
Centaurea/chemistry , Flavonoids/pharmacology , Plant Extracts/pharmacology , Sesquiterpenes/pharmacology , Xanthine Oxidase/antagonists & inhibitors , Enzyme Assays , Flavonoids/isolation & purification , Free Radical Scavengers/isolation & purification , Free Radical Scavengers/pharmacology , Plant Extracts/chemistry , Sesquiterpenes/isolation & purification
9.
J Nat Prod ; 79(10): 2658-2666, 2016 10 28.
Article in English | MEDLINE | ID: mdl-27731641

ABSTRACT

Human platelets contain conventional (α and ß) and novel isoforms of PKC (δ and θ), and PKC activation can result in platelet aggregation and secretion reaction that are important for thrombus formation. Several tumor-promoting Euphorbiaceae diterpenes are known to act as direct activators of PKC, but many types of such diterpenes have not been studied as platelet stimulators. In the present study, two new and five known phorbol esters were isolated from Euphorbia grandicornis. Two of the isolated phorbol esters together with compounds representing ingenane, jatrophane, and myrsinane structural types were studied on PKC activation and platelet stimulation. The investigated phorbol esters and ingenane esters induced blood platelet aggregation and ATP secretion. PKC activation was demonstrated by inducing membrane translocation of PKCs, phosphorylation of PKC substrates, and activation of PKC signaling pathways. The PKC-activating effect of the compounds correlated well with their efficacy to cause platelet stimulation. Moreover, by using an isoform-specific PKC inhibitor, it was found that besides conventional PKCs novel PKCs also play a positive role in platelet activation caused by phorbol/ingenane esters, especially in regulating platelet aggregation. The present results suggest that platelets afford a useful model for studying PKC activators of natural origin or their chemical derivatives.


Subject(s)
Blood Platelets/drug effects , Diterpenes/isolation & purification , Diterpenes/pharmacology , Euphorbia/chemistry , Protein Kinase C/drug effects , Diterpenes/chemistry , Humans , Hungary , Molecular Structure , Phosphorylation , Plant Components, Aerial/chemistry , Platelet Aggregation/drug effects , Protein Isoforms , Protein Kinase C/metabolism , Signal Transduction/drug effects
10.
J Nat Prod ; 79(8): 1990-2004, 2016 08 26.
Article in English | MEDLINE | ID: mdl-27441737

ABSTRACT

GIRK channels are activated by a large number of G protein-coupled receptors and regulate the electrical activity of neurons, cardiac atrial myocytes, and ß-pancreatic cells. Abnormalities in GIRK channel function have been implicated in the pathophysiology of neuropathic pain, drug addiction, and cardiac arrhythmias. In the heart, GIRK channels are selectively expressed in the atrium, and their activation inhibits pacemaker activity, thereby slowing the heart rate. In the present study, 19 new diterpenes, falcatins A-S (1-19), and the known euphorprolitherin D (20) were isolated from Euphorbia falcata. The compounds were assayed on stable transfected HEK-hERG (Kv11.1) and HEK-GIRK1/4 (Kir3.1 and Kir3.4) cells. Blocking activity on GIRK channels was exerted by 13 compounds (61-83% at 10 µM), and, among them, five possessed low potency on the hERG channel (4-20% at 10 µM). These selective activities suggest that myrsinane-related diterpenes are potential lead compounds for the treatment of atrial fibrillation.


Subject(s)
Diterpenes , Euphorbia/chemistry , G Protein-Coupled Inwardly-Rectifying Potassium Channels/drug effects , Potassium Channel Blockers , Animals , Diterpenes/chemistry , Diterpenes/classification , Diterpenes/isolation & purification , Diterpenes/pharmacology , G Protein-Coupled Inwardly-Rectifying Potassium Channels/classification , Heart , Membrane Potentials/drug effects , Molecular Structure , Neurons/metabolism , Potassium Channel Blockers/pharmacology , Receptors, G-Protein-Coupled
11.
Planta Med ; 81(14): 1270-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26383017

ABSTRACT

The present study focused on the investigation of the inhibition of cyclooxygenase-2 and nuclear factor kappa B1 gene expression, nitric oxide production, leukotriene biosynthesis (5-lipoxygenase), and cyclooxygenase-1 and cyclooxygenase-2 enzymes of Onopordum acanthium, and the isolation and identification of its active compounds. From the chloroform soluble part of the MeOH extract prepared from aerial parts, lignans [pinoresinol (1), syringaresinol (2), and medioresinol (3)] and flavonoids [hispidulin (4), nepetin (5), apigenin (6), and luteolin (7)] were isolated by a combination of different chromatographic methods. The structures of the compounds were determined by means of mass spectrometry and 1D- and 2D-nuclear magnetic resonance spectroscopy, and by comparison of the spectral data with literature values. Extracts of different polarity and the isolated compounds obtained from the aerial parts, together with those previously isolated from the roots of the plant [4ß,15-dihydro-3-dehydrozaluzanin C (8), zaluzanin C (9), 4ß,15,11ß,13-tetrahydrozaluzanin C (10), nitidanin diisovalerianate (11), 24-methylenecholesterol (12), and 13-oxo-9Z,11E-octadecadienoic acid (13)], were evaluated for their inhibitory effects on cyclooxygenase-2 and nuclear factor kappa B1 gene expression, inducible nitric oxide synthase, 5-lipoxygenase, and cyclooxygenase-1 and cyclooxygenase-2 enzymes in in vitro assays. It was found that O. acanthium extracts exert strong inhibitory activities in vitro and some lignans, flavonoids, and sesquiterpenes may play a role in these activities. 4ß,15-Dihydro-3-dehydrozaluzanin C and zaluzanin C at 20 µM were the most active constituents tested against lipopolysaccharide/interferon-γ-induced nitric oxide production (100.4 ± 0.5 % and 99.4 ± 0.8 %) in the inhibition of cyclooxygenase-2 (98.6 ± 0.2 % and 97.0 ± 1.1 %) and nuclear factor kappa B1 gene expression (76.7 ± 7.3 % and 69.9 ± 3.4 %). Furthermore, it was shown that these inhibitory effects are not due to cytotoxicity of the compounds.


Subject(s)
Cyclooxygenase Inhibitors/pharmacology , NF-kappa B p50 Subunit/genetics , Nitric Oxide/metabolism , Onopordum/chemistry , Plant Extracts/pharmacology , Arachidonate 5-Lipoxygenase/genetics , Arachidonate 5-Lipoxygenase/metabolism , Cell Line/drug effects , Cyclooxygenase 1/genetics , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase Inhibitors/chemistry , Drug Evaluation, Preclinical/methods , Gene Expression Regulation/drug effects , Humans , Lipoxygenase Inhibitors/chemistry , Lipoxygenase Inhibitors/pharmacology , Molecular Structure , NF-kappa B p50 Subunit/antagonists & inhibitors , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/chemistry , Plants, Medicinal/chemistry
12.
Chem Biodivers ; 12(8): 1214-21, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26265573

ABSTRACT

Phytochemical investigation of the MeOH extract obtained from the aerial parts of the annual weed Euphorbia exigua L. resulted in the isolation of two novel (1, 2) and one known (3) jatrophane diterpenes. Their structures were established by extensive 1D- and 2D-NMR spectroscopy and HR-ESI-MS. The isolated compounds were evaluated for multidrug resistance (MDR) reversing activity on human MDR gene-transfected L5178 mouse lymphoma cells; and all three compounds were found to modulate the intracellular drug accumulation.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Diterpenes/chemistry , Diterpenes/pharmacology , Drug Resistance, Multiple/drug effects , Euphorbia/chemistry , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Animals , Cell Line, Tumor , Diterpenes/isolation & purification , Drug Resistance, Neoplasm/drug effects , Humans , Lymphoma/drug therapy , Lymphoma/genetics , Lymphoma/metabolism , Mice , Transfection
13.
J Nat Prod ; 77(12): 2641-50, 2014 Dec 26.
Article in English | MEDLINE | ID: mdl-25479041

ABSTRACT

Two new arylbenzofuran-type neolignans, 1"-dehydroegonol 3"-methyl ether (1) and egonol 3"-methyl ether (2), and four known lignan derivatives, namely, helioxanthin (3), (7E)-7,8-dehydroheliobuphthalmin (4), heliobuphthalmin (5), and 7-acetoxyhinokinin (6), were isolated from a chloroform-soluble partition of the methanol extract of the fresh roots of Heliopsis helianthoides var. scabra. These six compounds were evaluated in vitro in terms of their ability to inhibit the various steps involved in brain tumor metastasis formation. Compounds 3 and 4 inhibited the migration of both melanoma and brain endothelial cells, and 3 also reduced the adhesion of melanoma cells to the brain endothelium. Furthermore, 3 and 4 additionally enhanced the barrier function of the blood-brain barrier and the expression of the tight junction protein ZO-1 at the junctions of the endothelial cells. These findings suggest that 3 and 4 may have the potential to interfere with different steps of brain metastasis formation and to enhance the barrier function of cerebral endothelial cells.


Subject(s)
Asteraceae/chemistry , Brain/drug effects , Lignans/isolation & purification , Lignans/pharmacology , Actin Cytoskeleton , Animals , Blood-Brain Barrier/metabolism , Brain/metabolism , Cell Survival/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Humans , Hungary , Lignans/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Roots/chemistry , Rats , Zonula Occludens-1 Protein/drug effects
14.
Dalton Trans ; 43(48): 17971-9, 2014 Dec 28.
Article in English | MEDLINE | ID: mdl-25359218

ABSTRACT

The identity of the predominating tin(ii)-hydroxide complex formed in hyper-alkaline aqueous solutions (0.2 ≤CNaOH≤ 12 mol dm(-3)) is determined by potentiometric titrations, Raman, Mössbauer and XANES spectroscopy, supplemented by quantum chemical calculations. Thermodynamic studies using a H2/Pt electrode up to free hydroxide concentrations of 1 mol dm(-3) showed the presence of a single monomeric complex with a tin(II) : hydroxide ratio of 1 : 3. This observation together with Raman and Mössbauer spectroscopic measurements supplemented by quantum mechanical calculations proved that the predominating complex is [Sn(OH)3](-), and that the presence of the other possible complex, [SnO(OH)](-), could not be proven with either experiments or simulations. The structure of the trihydroxidostannate(II) complex, [Sn(OH)3](-), was determined by EXAFS and was found to be independent of the applied hydroxide and tin(II) concentrations. The mean Sn-O bond distance is short, 2.078 Å, and in very good agreement with the only structure reported in the solid state. It is also shown that at pH values above 13 the speciation of the predominant trihydroxidostannate(II) complex is not affected by the presence of high concentrations of chloride ions.


Subject(s)
Hydroxides/chemistry , Tin/chemistry , Coordination Complexes/chemistry , Quantum Theory , Spectroscopy, Mossbauer , Spectrum Analysis, Raman , Thermodynamics , Water/chemistry , X-Ray Absorption Spectroscopy
15.
Planta Med ; 80(18): 1692-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25295671

ABSTRACT

The extract of Artemisia asiatica herb with antiproliferative activity against four human tumor cell lines (A2780, A431, HeLa, and MCF7) was analyzed by the MTT assay, and bioassay-directed fractionation was carried out in order to identify the compounds responsible for the cytotoxic activity. Guaianolide (1-4), seco-guianolide (5), germacranolide (6) and eudesmanolide sesquiterpenes (7), monoterpenes (8, 9), including the new compound artemisia alcohol glucoside (8), and flavonoids (10-16) were isolated as a result of a multistep chromatographic procedure (CC, CPC, PLC, and gel filtration). The compounds were identified by means of UV, MS, and NMR spectroscopy, including (1)H-and (13)C-NMR, (1)H-(1)H COSY, NOESY, HSQC, and HMBC experiments. The isolated compounds 1-16 were evaluated for their tumor cell growth-inhibitory activities on a panel of four adherent cancer cell lines, and different types of secondary metabolites were found to be responsible for the cytotoxic effects of the extract. Especially cirsilineol (13), 3ß-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (3), and iso-seco-tanapartholide 3-O-methyl ester (5) exerted marked cytotoxic effects against the investigated cell lines, while jaceosidin (12), 6-methoxytricin (15), artecanin (2), and 5,7,4',5'-tetrahydroxy-6,3'-dimethoxyflavone (14) were moderately active. All the sesquiterpenes and monoterpenes are reported here for the first time from this species, and in the case of artecanin (2), 3α-chloro-4ß,10α-dihydroxy-1ß,2ß-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (4), ridentin (6), and ridentin B (7), previously unreported NMR spectroscopic data were determined.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Artemisia/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor/drug effects , Drug Screening Assays, Antitumor , Flavones/chemistry , Flavones/isolation & purification , Flavones/pharmacology , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Sesquiterpenes, Germacrane/chemistry , Sesquiterpenes, Germacrane/isolation & purification , Sesquiterpenes, Germacrane/pharmacology
16.
CNS Neurol Disord Drug Targets ; 13(8): 1458-64, 2014.
Article in English | MEDLINE | ID: mdl-25345505

ABSTRACT

There is heightened interest in the field of stroke recovery as there is need for agents that would prevent the debilitating effects of the disorder, thereby tremendously reducing the societal and economic costs associated with it. In this study, the isolation of two flavonoids--quercetin-3-O-galactoside (1) and quercetin-3-O-arabinoside (2)--from Rumex aquaticus (western dock) and their neuroprotective effects were reported in the oxygen-glucose deprivation (OGD) model of in vitro ischemia using rat pheochromocytoma (PC12) cell line. Bioassay-guided fractionation of the ethyl-acetate extract of Rumex aquaticus L. afforded the isolation of compounds 1 and 2. The structures of compounds were established on the basis of spectroscopic analyses (UV, mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). Both compounds were isolated for the first time from this species. In the course of the pharmacological experiments it was detected that these flavonoids at 10 µM concentration significantly improved cell survival in the oxygen-glucose deprivation model of ischemia. Moreover, they also increased neurite outgrowth in differentiated PC12 cells subjected to ischemic insult. Investigations on the cellular mechanism for the observed effect revealed that compound 1 (10 µM) enhances the expression of synaptophysin - a marker of synapses, and an indicator of synaptic plasticity. Rapid restoration of neurological function following injury is paramount to the prevention of debilitating consequences of ischemic stroke. This combination of neuroprotection and neuritogenic potential could be particularly useful in the recovery phase of stroke.


Subject(s)
Flavonoids/pharmacology , Gene Expression Regulation/drug effects , Neurites/drug effects , Neuroprostanes/pharmacology , Rumex/chemistry , Synaptophysin/metabolism , Actins/metabolism , Animals , Cell Death/drug effects , Dose-Response Relationship, Drug , Glucose/deficiency , Hypoxia , PC12 Cells/cytology , PC12 Cells/drug effects , Plant Extracts/chemistry , Rats
17.
Toxins (Basel) ; 6(9): 2857-71, 2014 Sep 23.
Article in English | MEDLINE | ID: mdl-25251540

ABSTRACT

Bipolaris oryzae is a phytopathogenic fungus causing a brown spot disease in rice, and produces substance that strongly perturbs motility and membrane integrities of boar spermatozoa. The substance was isolated from the liquid culture of the fungal strain using extraction and a multi-step semi-preparative HPLC procedures. Based on the results of mass spectrometric and 2D NMR techniques, the bioactive molecule was identified as ophiobolin A, a previously described sesterterpene-type compound. The purified ophiobolin A exhibited strong motility inhibition and viability reduction on boar spermatozoa. Furthermore, it damaged the sperm mitochondria significantly at sublethal concentration by the dissipation of transmembrane potential in the mitochondrial inner membrane, while the plasma membrane permeability barrier remained intact. The study demonstrated that the cytotoxicity of ophiobolin A toward somatic cell lines is higher by 1-2 orders of magnitude compared to other mitochondriotoxic mycotoxins, and towards sperm cells unique by replacing the progressive motility by shivering tail beating at low exposure concentration.


Subject(s)
Ascomycota , Sesterterpenes/toxicity , Sperm Motility/drug effects , Spermatozoa/drug effects , Animals , Cats , Cell Death/drug effects , Cell Line , Cell Line, Tumor , Cell Membrane Permeability/drug effects , Male , Mice , Spermatozoa/physiology , Swine
18.
J Nat Prod ; 77(7): 1663-9, 2014 Jul 25.
Article in English | MEDLINE | ID: mdl-24972328

ABSTRACT

The discovery of the interaction of plant-derived N-alkylamides (NAAs) and the mammalian endocannabinoid system (ECS) and the existence of a plant endogenous N-acylethanolamine signaling system have led to the re-evaluation of this group of compounds. Herein, the isolation of seven NAAs and the assessment of their effects on major protein targets in the ECS network are reported. Four NAAs, octadeca-2E,4E,8E,10Z,14Z-pentaene-12-ynoic acid isobutylamide (1), octadeca-2E,4E,8E,10Z,14Z-pentaene-12-ynoic acid 2'-methylbutylamide (2), hexadeca-2E,4E,9Z-triene-12,14-diynoic acid isobutylamide (3), and hexadeca-2E,4E,9,12-tetraenoic acid 2'-methylbutylamide (4), were identified from Heliopsis helianthoides var. scabra. Compounds 2-4 are new natural products, while 1 was isolated for the first time from this species. The previously described macamides, N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide (5), N-benzyl-(9Z,12Z,15Z)-octadecatrienamide (6), and N-benzyl-(9Z,12Z)-octadecadienamide (7), were isolated from Lepidium meyenii (Maca). N-Methylbutylamide 4 and N-benzylamide 7 showed submicromolar and selective binding affinities for the cannabinoid CB1 receptor (Ki values of 0.31 and 0.48 µM, respectively). Notably, compound 7 also exhibited weak fatty acid amide hydrolase (FAAH) inhibition (IC50 = 4 µM) and a potent inhibition of anandamide cellular uptake (IC50 = 0.67 µM) that was stronger than the inhibition obtained with the controls OMDM-2 and UCM707. The pronounced ECS polypharmacology of compound 7 highlights the potential involvement of the arachidonoyl-mimicking 9Z,12Z double-bond system in the linoleoyl group for the overall cannabimimetic action of NAAs. This study provides additional strong evidence of the endocannabinoid substrate mimicking of plant-derived NAAs and uncovers a direct and indirect cannabimimetic action of the Peruvian Maca root.


Subject(s)
Arachidonic Acids/isolation & purification , Asteraceae/chemistry , Furans/isolation & purification , Lepidium/chemistry , Polyunsaturated Alkamides/isolation & purification , Amidohydrolases/metabolism , Animals , Arachidonic Acids/chemistry , Arachidonic Acids/metabolism , Ethanolamines/metabolism , Furans/chemistry , Furans/metabolism , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Peru , Plant Roots/chemistry , Polyunsaturated Alkamides/chemistry , Polyunsaturated Alkamides/metabolism
19.
Nat Prod Commun ; 9(3): 337-40, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24689209

ABSTRACT

Onopordum acanthium has been considered in traditional medicine to be effective against different cancers. The chloroform extracts of the root, which displayed antiproliferative effect against human tumor cell lines, was subjected to bioactivity-guided multistep chromatographic separation. This experiment resulted in the isolation of the sesquiterpene lactones 4beta,14-dihydro-3-dehydrozaluzanin C (1), zaluzanin C (2) and 4beta,15,11beta,13-tetrahydrozaluzanin C (3), the neolignan nitidanin-diisovalerianate (4), besides 13-oxo-9Z,11 E-octadecadienoic acid (5), 24-methylenecholesterol (6), alpha-linolenic acid, linoleic acid, stigmasterol and beta-sitosterol. The structures of the isolated compounds were established through analytical data (NMR, MS), and by comparison of these with those reported in the literature. All the aforementioned compounds were detected for the first time from this plant. The antiproliferative activities of compounds 1-6 were assessed on cervix adenocarcinoma HeLa, breast adenocarcinoma MCF7 and skin epidermoid carcinoma A431 cells by using the MTT assay. It was found that, 4beta,14-dihydro-3-dehydrozaluzanin C (1), the most active antiproliferative compound of the extract, exerted remarkable tumor cell growth inhibitory activity (IC50 2.7-15.1 microM).


Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Onopordum/chemistry , Drug Screening Assays, Antitumor , HeLa Cells , Humans , MCF-7 Cells , Plant Roots/chemistry
20.
J Nat Prod ; 77(3): 576-82, 2014 Mar 28.
Article in English | MEDLINE | ID: mdl-24476550

ABSTRACT

Five new sesquiterpenes, neurolobatin A (1), neurolobatin B (2), 5ß-hydroxy-8ß-isovaleroyloxy-9α-hydroxycalyculatolide (3), 3-epi-desacetylisovaleroylheliangine (4), and 3ß-acetoxy-8ß-isovaleroyloxyreynosin (5), were isolated from the aerial parts of Neurolaena lobata. The structures were established by means of a combined spectroscopic data analysis, including ESIMS, APCI-MS, and 1D- and 2D-NMR techniques. Neurolobatin A (1) and B (2) are unusual isomeric seco-germacranolide sesquiterpenes with a bicyclic acetal moiety, compounds 3 and 4 are unsaturated epoxy-germacranolide esters, and compound 5 is the first eudesmanolide isolated from the genus Neurolaena. The isolated compounds (1-5) were shown to have noteworthy antiproliferative activities against human tumor cell lines (A2780, A431, HeLa, and MCF7). The anti-inflammatory effects of 1-5, evaluated in vitro using LPS- and TNF-α-induced IL-8 expression inhibitory assays, revealed that all these compounds strongly down-regulated the LPS-induced production of IL-8 protein, with neurolobatin B (2) and 3-epi-desacetylisovaleroylheliangine (4) being the most effective.


Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Asteraceae/chemistry , Sesquiterpenes, Germacrane/isolation & purification , Sesquiterpenes, Germacrane/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Drug Screening Assays, Antitumor , Female , Guatemala , HeLa Cells , Humans , Interleukin-8/metabolism , Lipopolysaccharides/pharmacology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Sesquiterpenes, Germacrane/chemistry , Tumor Necrosis Factor-alpha/pharmacology , Umbilical Veins/cytology , Umbilical Veins/drug effects
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