ABSTRACT
Plants of the Amaryllidaceae family are promising therapeutic tools for human diseases and have been used as alternative medicines. The specific secondary metabolites of this plant family, called Amaryllidaceae alkaloids (AA), have attracted considerable attention due to their interesting pharmacological activities. One of them, galantamine, is already used in the therapy of Alzheimer's disease as a long acting, selective, reversible inhibitor of acetylcholinesterase. One group of AA is the montanine-type, such as montanine, pancracine and others, which share a 5,11-methanomorphanthridine core. So far, only 14 montanine-type alkaloids have been isolated. Compared with other structural-types of AA, montanine-type alkaloids are predominantly present in plants in low concentrations, but some of them display promising biological properties, especially in vitro cytotoxic activity against different cancerous cell lines. The present review aims to summarize comprehensively the research that has been published on the Amaryllidaceae alkaloids of montanine-type.
Subject(s)
Amaryllidaceae Alkaloids/chemistry , Amaryllidaceae/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antiprotozoal Agents/chemistry , Cholinesterase Inhibitors/chemistry , Nootropic Agents/chemistry , Amaryllidaceae/metabolism , Amaryllidaceae Alkaloids/isolation & purification , Amaryllidaceae Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Antiprotozoal Agents/isolation & purification , Antiprotozoal Agents/pharmacology , Cell Line, Tumor , Cholinesterase Inhibitors/isolation & purification , Cholinesterase Inhibitors/pharmacology , Galantamine/chemistry , Galantamine/isolation & purification , Galantamine/pharmacology , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Inhibitory Concentration 50 , Isoquinolines/chemistry , Isoquinolines/isolation & purification , Isoquinolines/pharmacology , Nootropic Agents/isolation & purification , Nootropic Agents/pharmacology , Phenanthridines/chemistry , Phenanthridines/isolation & purification , Phenanthridines/pharmacology , Plant Extracts/chemistry , Secondary MetabolismABSTRACT
Astragalus ernestii has been used as a substitute for Radix Astragali (Huang-Qi) in southwest China. To better understand the chemical rationale for the medicinal usage, the phytochemistry of A. ernestii was recently studied. As a result, a novel aurone-phenylpropanoid adduct astrernestin (1), together with five known phenoloids calycosin-7-O-ß-D-glucopyranoside (2), 4,4'-dimethoxy-3'-hydroxy-7,9':7',9-diepoxylignan-3-O-ß-D-glucopyranoside (3), syringaresinol-4-O-ß-D-monoglucoside (4), hedyotol D 4â³-O-ß-D-glucopyranoside (5) and trifolirhizin (6), were isolated from the roots of A. ernestii. The structure of compound 1 was elucidated by extensive spectroscopic analysis and optical rotation calculation.
Subject(s)
Astragalus Plant/chemistry , Benzofurans/chemistry , Phenols/chemistry , Plant Roots/chemistry , Astragalus propinquus , China , Drugs, Chinese Herbal , Furans/isolation & purification , Glucosides/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Isoflavones/isolation & purification , Lignans/isolation & purification , Molecular Structure , Phenols/isolation & purificationABSTRACT
Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the aerial parts and roots of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC50 value of 0.525⯱â¯0.140⯵M, which was comparable with the positive control, huperzine A (IC50â¯=â¯0.143⯱â¯0.029⯵M).
Subject(s)
Alkaloids/pharmacology , Cholinesterase Inhibitors/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Lycopodiaceae/chemistry , Alkaloids/isolation & purification , China , Cholinesterase Inhibitors/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Components, Aerial/chemistry , Plant Roots/chemistryABSTRACT
Cissampelos sympodialis Eichler is well studied and investigated for its antiasthmatic properties, but there are no data in the literature describing antibacterial properties of alkaloids isolated from this botanical species. This work reports the isolation and characterization of phanostenine obtained from roots of C. sympodialis and describes for the first time its antimicrobial and antibiotic modulatory properties. Phanostenine was first isolated from Cissampelos sympodialis and its antibacterial activities were determined. Chemical structures of the alkaloid isolate were determined using spectroscopic and chemical analyses. Phanostenine was also tested for its antibacterial activity against standard strains and clinical isolates of Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentration (MIC) was determined in a microdilution assay and for the evaluation of antibiotic resistance-modifying activity. MIC of the antibiotics was determined in the presence or absence of phanostenine at sub-inhibitory concentrations. The evaluation of antibacterial activity by microdilution assay showed activity for all strains with better values against S. aureus ATCC 12692 and E. coli 27 (787.69â mm). The evaluation of aminoglycoside antibiotic resistance-modifying activity showed reduction in the MIC of the aminoglycosides (amikacin, gentamicin and neomycin) when associated with phanostenine, MIC reduction of antibiotics ranging from 21 % to 80 %. The data demonstrated that phanostenine possesses a relevant ability to modify the antibiotic activity inâ vitro. We can suggest that phanostenine presents itself as a promising tool as an adjuvant for novel antibiotics formulations against bacterial resistance.
Subject(s)
Alkaloids/chemistry , Anti-Bacterial Agents/chemistry , Benzene Derivatives/chemistry , Cissampelos/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Benzene Derivatives/isolation & purification , Benzene Derivatives/pharmacology , Cissampelos/metabolism , Drug Resistance, Bacterial/drug effects , Fused-Ring Compounds , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Heterocyclic Compounds, 4 or More Rings/pharmacology , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Roots/chemistry , Plant Roots/metabolism , Staphylococcus aureus/drug effectsABSTRACT
A chemical investigation on the 70% EtOH extract of the aerial parts of Lycopodiastrum casuarinoides led to the isolation of six novel lycodine type alkaloids, lycocasuarines A-F (1-6). The structures of the isolated compounds were established based on 1D and 2D (1H1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated alkaloids were tested in vitro for cytotoxic potentials against seven malignant melanoma cell lines as well as acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities. As a result, alkaloids 1 and 3 exhibited significant cytotoxic activities against all the tested tumor cell lines with IC50 values <10⯵M and the inhibitory activities for AchE (0.94⯱â¯0.15 and 0.24⯱â¯0.03⯵M, respectively) and BuchE (1.82⯱â¯0.12 and 7.31⯱â¯0.42⯵M, respectively).
Subject(s)
Alkaloids/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Cholinesterase Inhibitors/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Lycopodiaceae/chemistry , Acetylcholinesterase , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Butyrylcholinesterase , Cell Line, Tumor , Cholinesterase Inhibitors/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Components, Aerial/chemistryABSTRACT
In the endeavor to obtain new antitrypanosomal agents, particularly sesquiterpene lactones, from Kenyan plants of the family Asteraceae, Vernonia cinerascens Sch. Bip. was investigated. Bioactivity-guided fractionation and isolation in conjunction with LC/MS-based dereplication has led to the identification of vernodalol (1) and isolation of vernodalin (2), 11ß,13-dihydrovernodalin (3), 11ß,13-dihydrovernolide (4), vernolide (5), 11ß,13-dihydrohydroxyvernolide (6), hydroxyvernolide (7), and a new germacrolide type sesquiterpene lactone vernocinerascolide (8) from the dichloromethane extract of V. cinerascens leaves. Compounds 3-8 were characterized by extensive analysis of their 1D and 2D NMR spectroscopic and HR/MS spectrometric data. All the compounds were evaluated for their in vitro biological activity against bloodstream forms of Trypanosoma brucei rhodesiense and for cytotoxicity against the mammalian cell line L6. Vernodalin (2) was the most active compound with an IC50 value of 0.16 µM and a selectivity index of 35. Its closely related congener 11ß,13-dihydrovernodalin (3) registered an IC50 value of 1.1 µM and a selectivity index of 4.2.
Subject(s)
Lactones/pharmacology , Sesquiterpenes/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma brucei rhodesiense/drug effects , Vernonia/chemistry , Animals , Cell Line, Transformed , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Heterocyclic Compounds, 4 or More Rings/pharmacology , Inhibitory Concentration 50 , Lactones/isolation & purification , Myoblasts/cytology , Myoblasts/drug effects , Myoblasts/physiology , Plant Extracts/chemistry , Plant Leaves/chemistry , Rats , Sesquiterpenes/isolation & purification , Trypanocidal Agents/isolation & purification , Trypanosoma brucei rhodesiense/growth & developmentABSTRACT
Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels. Following liquid chromatography-tandem mass analysis of the DIOB content of DB extract, male ICR mice were randomly orally administered DB or DIOB for 14days. Liver injury was assessed by histopathological and biochemical analysis of liver fuction. The levels of transporter protein and mRNA were determined by western blotting and real-time PCR. Liver function and histopathological analysis indicated that both DB and DIOB could induce liver injury in mice, and that DIOB might be the primary toxic compound in DB. Moreover, down-regulation of Mrp2 blocked the excretion of bilirubin, glutathione disulfide, and bile acids, leading to the accumulation of toxic substrates in the liver and a redox imbalance. We identified down-regulated expression of Mrp2 as potential factors linked to increased serum bilirubin levels and decreased levels of glutathione in the liver and increased liver injury severity. In summary, our study indicates that down-regulation of Mrp2 represents the primary mechanism of DB- and DIOB-induced hepatotoxicity, and provides insight into novel therapies that could be used to prevent DB- and DIOB-mediated liver injury.
Subject(s)
ATP-Binding Cassette Transporters/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Dioscorea/chemistry , Drugs, Chinese Herbal/toxicity , Heterocyclic Compounds, 4 or More Rings/toxicity , Multidrug Resistance-Associated Proteins/metabolism , Organic Anion Transporters, Sodium-Dependent/metabolism , Organic Cation Transport Proteins/metabolism , Symporters/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 11 , ATP-Binding Cassette Transporters/genetics , Animals , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/pathology , Drugs, Chinese Herbal/isolation & purification , Gene Expression/drug effects , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Mice, Inbred ICR , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/genetics , Organic Anion Transporters, Sodium-Dependent/genetics , Organic Cation Transport Proteins/genetics , Symporters/geneticsABSTRACT
The phytochemical study of Stereocaulon montagneanum harvested in Sumatra (Indonesia) led to the isolation of 11 known compounds including two metabolites not previously described in the genus Stereocaulon, peristictic acid (8) and menegazziaic acid (10). The complete 1H and 13C NMR spectral assignments of stictic acid derivatives are reported with some revisions. Five depsidones belonging to the stictic acid chemosyndrome were superoxide anion scavengers as potent as ascorbic acid and with no toxicity on two human cell lines.
Subject(s)
Antioxidants/pharmacology , Free Radical Scavengers/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Lichens/chemistry , Oxepins/pharmacology , Radiation-Protective Agents/pharmacology , Superoxides/metabolism , Animals , Antioxidants/chemistry , Antioxidants/isolation & purification , Cell Line , Drug Evaluation, Preclinical , Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Humans , Indonesia , Keratinocytes/drug effects , Keratinocytes/radiation effects , Melanoma, Experimental , Mice , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Oxepins/chemistry , Oxepins/isolation & purification , Radiation-Protective Agents/chemistry , Radiation-Protective Agents/isolation & purification , Solvents , Ultraviolet RaysABSTRACT
The ethanol extract from Inula salsoloides (Turcz.) Ostenf was found to cause high mortality against Plutella xylostella L. (Lepidoptera: Plutellidae). The active components were isolated and identified. Two compounds were obtained and identified to be inulasalsolin and taraxasterol. Both compounds showed anti-feedant effects against third instar larvae of P. xylostella with AFC50 of 0.030 and 0.053 mg/mL and insecticidal activities with LC50 of 0.19 and 0.49 mg/mL, respectively. The two compounds also exhibited high toxicity to cabbage aphid, Brevicoryne brassicae L. (Hemiptera: Aphididae) with LC50 values of 0.021 and 0.098 mg/mL. This is the first report on the study of insecticidal components of I. salsoloides and their activity against insects.
Subject(s)
Heterocyclic Compounds, 4 or More Rings/pharmacology , Insecticides/pharmacology , Inula/chemistry , Sterols/pharmacology , Triterpenes/pharmacology , Animals , Aphids/drug effects , Drug Evaluation, Preclinical/methods , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Insecticides/chemistry , Insecticides/isolation & purification , Larva/drug effects , Lepidoptera/drug effects , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/pharmacology , Sterols/chemistry , Triterpenes/chemistryABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of M. koenigii Linn. Spreng (Rutaceae) have been used as traditional medicine for anxiety disorders. Aim of the study was to isolate antianxiety principle(s) from the leaves of M. koenigii using bioactivity guided approach. MATERIAL AND METHODS: Hydroalcoholic extract of M. koenigii leaves was prepared using soxhlet apparatus, and the same was evaluated for antianxiety activity at 250, 500 and 750mg/kg, po, using Elevated plus-maze (EPM). The extract was further partitioned successively with pet ether, chloroform, ethyl acetate and 1-butanol. All the fractions were evaluated for antianxiety activity. The bioactive ethyl acetate fraction was column chromatographed to get 5 fractions (F1-F5). All the fractions were evaluated for antianxiety activity using EPM. A pure compound, separated out from F2, was characterized using standard spectroscopic techniques, and its anxiolytic activity was evaluated using EPM. Antianxiety activity of isolated compound was further evaluated using Actophotometer and m-CPP induced anxiety model. TLC-densitometric method was developed to quantify mahanimbine in the plant. RESULTS: The present study resulted in the isolation of mahanimbine, which exhibits potent antianxiety activity at 3mg/kg, and the activity was statistically comparable to that of diazepam (2mg/kg). The developed TLC-densitometric method is specific, linear, precise, accurate, repeatable and robust. CONCLUSIONS: This study validates the ethnopharmacological use of M. koenigii leaves in the management of anxiety disorders. Mahanimbine is responsible for the antianxiety effect of M. koenigii leaves.
Subject(s)
Anti-Anxiety Agents/pharmacology , Anxiety/drug therapy , Carbazoles/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Murraya/chemistry , Plant Leaves/chemistry , Animals , Anti-Anxiety Agents/isolation & purification , Anti-Anxiety Agents/toxicity , Anxiety/psychology , Carbazoles/isolation & purification , Carbazoles/toxicity , Disease Models, Animal , Female , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Heterocyclic Compounds, 4 or More Rings/toxicity , Male , Maze Learning/drug effects , Mice, Inbred Strains , Molecular Structure , Motor Activity/drug effects , Toxicity Tests, AcuteABSTRACT
Two new Lycopodium alkaloids, squarrosine A (1) and pyrrolhuperzine A (2), were isolated from the Thai and Philippine plant Huperzia squarrosa. (R)-2-Piperidineacetic acid (5) was a known alkaloid, but has now been isolated for the first time from a natural source. Their structures were elucidated using extensive spectroscopic analyses and, for pyrrolhuperzine A (2), confirmation by chemical transformation. The new compounds exhibited moderate acetylcholinesterase inhibitory activities.
Subject(s)
Alkaloids/isolation & purification , Cholinesterase Inhibitors/isolation & purification , Heterocyclic Compounds, 3-Ring/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Huperzia/chemistry , Plant Extracts/isolation & purification , Acetylcholinesterase , Alkaloids/chemistry , Alkaloids/pharmacology , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/pharmacology , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Molecular Structure , Philippines , Plant Extracts/chemistry , Plant Extracts/pharmacology , ThailandABSTRACT
Peltomexicanin (7,10-dihydroxy-6,12-dioxa-5H-tetraphen-3-one) is a new peltogynoid quinone methide isolated from Palo Morado (Peltogyne mexicana Martínez) heartwood by column chromatography. Its chemical structure was elucidated by IR, NMR (¹H, (13)C), 2D NMR experiments (COSY, NOESY, HMQC, and HSQC), ESI-MS, and UV-Vis spectroscopic analysis. According to HPLC quantification, this compound is the main pigment and accounts for 1.21% of Palo Morado heartwood material. The antioxidant activity of peltomexicanin and dried methanolic extract (DEx) of purple heartwood was evaluated using the radical of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and the corresponding values expressed as Trolox equivalents (µmol TE/mg sample) were 4.25 and 4.57, respectively.
Subject(s)
Free Radical Scavengers/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Plant Extracts/chemistry , Benzothiazoles/chemistry , Chromatography, High Pressure Liquid , Fabaceae/chemistry , Free Radical Scavengers/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Molecular Structure , Plant Extracts/isolation & purification , Sulfonic Acids/chemistry , Wood/chemistryABSTRACT
Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 µM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 µM.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cholinesterase Inhibitors/isolation & purification , Cholinesterase Inhibitors/pharmacology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Galantamine/isolation & purification , Galantamine/pharmacology , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Heterocyclic Compounds, 4 or More Rings/pharmacology , Liliaceae/chemistry , Plants, Medicinal/chemistry , Acetylcholinesterase/metabolism , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cholinesterase Inhibitors/chemistry , Crystallography, X-Ray , Drugs, Chinese Herbal/chemistry , Galantamine/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Inhibitory Concentration 50 , Medicine, Traditional , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, BiomolecularABSTRACT
CONTEXT: Dichapetalum filicaule Breteler (Dichapetalaceae) is a rare species occurring only in Côte d'Ivoire and Ghana. Although research on several species of the genus has produced interesting bioactive compounds, particularly the Dichapetalins, a novel class of triterpenoids with antineoplastic properties, there is virtually no information on the ethnobotanical uses and chemical constituents of D. filicaule. OBJECTIVE: The phytochemical and anthelminthic activities of the constituents of D. filicaule were investigated. MATERIALS AND METHODS: Chemical constituents of the petroleum ether, chloroform-acetone, and methanol root extracts of D. filicaule were isolated by column chromatography and characterized by their physico-chemical properties, 1-D and 2-D NMR spectroscopy and mass spectrometry. In vitro anthelminthic activity of the extracts and compounds against the human hookworm, Necator americanus, Stiles 1902 (Nematoda: Ancylostomatidae) was determined within a concentration range of 2500-250 µg/ml using the Egg Hatch Inhibition (EHI) Assay. The hookworm species were identified using a published polymerase chain reaction (PCR) method. RESULTS: A new dichapetalin, dichapetalin X (1), together with the known dichapetalin A (2), pomolic acid (3), glycerol monostearate (4), D:A-friedooleanan-3ß-ol (5), and D:A-friedooleanan-3-one (6) were isolated. Compounds 1, 2, and 4 exhibited EHI with IC50 values of 523.2, 162.4, and 306.0 µg/ml, respectively, against the hookworm. The positive control albendazole gave an IC50 value of 93.27 µg/ml. DISCUSSION AND CONCLUSION: This is the first report of the phytochemical investigation of D. filicaule. The study has yielded a new dichapetalin and also demonstrated the potential anthelminthic properties of the constituents.
Subject(s)
Anthelmintics/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Magnoliopsida , Necator americanus/drug effects , Plant Extracts/pharmacology , Spiro Compounds/pharmacology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Anthelmintics/isolation & purification , Child , Child, Preschool , Chromatography, Thin Layer , Female , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Humans , Magnetic Resonance Spectroscopy , Magnoliopsida/chemistry , Male , Mass Spectrometry , Middle Aged , Necator americanus/genetics , Necator americanus/growth & development , Parasite Egg Count , Parasitic Sensitivity Tests , Phytotherapy , Plant Extracts/isolation & purification , Plant Roots , Plants, Medicinal , Solvents/chemistry , Spiro Compounds/isolation & purification , Young AdultABSTRACT
The effects of the Securinega alkaloid (+)-phyllanthidine on Leishmania (L.) amazonensis and the first chemical investigation of Margaritaria nobilis L.f. (Phyllanthaceae) are described. Treating the parasites with this alkaloid caused a dose-dependent reduction in promastigote growth of 67.68% (IC50 82.37 µg/mL or 353 µM) and in amastigote growth of 83.96% (IC50 49.11 µg/mL or 210 µM), together with ultrastructural alterations in the promastigotes. No cytotoxic effect was detected in mammalian cells (CC50 1727.48 µg/mL or CC50 5268 µM). Classical chromatographic techniques and spectral methods led to the isolation and identification of betulinic acid, kaempferol, corilagin, gallic acid and its methyl ester, besides (+)-phyllanthidine from M. nobilis leaves and stems. Margaritaria nobilis is another source of the small group of Securinega alkaloids, together with other Phyllanthaceae (Euphorbiaceae s.l.) species. The low toxicity to macrophages and the effects against promastigotes and amastigotes are suggestive that (+)-phyllanthidine could be a promising antileishmanial agent for treating cutaneous leishmaniasis.
Subject(s)
Antiprotozoal Agents/pharmacology , Euphorbiaceae/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Leishmania braziliensis/drug effects , Life Cycle Stages/drug effects , Phytochemicals/pharmacology , Alkaloids/isolation & purification , Animals , Antiprotozoal Agents/isolation & purification , Dose-Response Relationship, Drug , Gallic Acid/isolation & purification , Glucosides/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Hydrolyzable Tannins/isolation & purification , Inhibitory Concentration 50 , Kaempferols/isolation & purification , Leishmania braziliensis/growth & development , Leishmania braziliensis/ultrastructure , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/parasitology , Male , Mice , Mice, Inbred BALB C , Pentacyclic Triterpenes , Phytochemicals/isolation & purification , Plant Extracts/chemistry , Primary Cell Culture , Triterpenes/isolation & purification , Betulinic AcidABSTRACT
BACKGROUND: The Chines herb derived Sparstolonin B, (SsnB), is a recently identified natural compound that selectively blocks TLR2- and TLR4-mediated inflammatory signaling. But it is unknown whether this compound has any effect on HIV infection. FINDINGS: We found that SsnB treatment blocked HIV-1 transcription via a novel mechanism that requires the TAR region. Treatment of human T cell lines or peripheral blood mononuclear cells with SsnB at 1 µM significantly inhibited HIV production. Lastly, SsnB was able to inhibit HIV in synergy with AZT. CONCLUSIONS: These data suggest that SsnB is a novel natural compound that inhibits HIV-1 transcription and may be a new drug in the treatment of HIV infection.
Subject(s)
Anti-HIV Agents/isolation & purification , Anti-HIV Agents/pharmacology , HIV-1/drug effects , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Heterocyclic Compounds, 4 or More Rings/pharmacology , Plants, Medicinal/chemistry , Transcription, Genetic/drug effects , Biological Products/isolation & purification , Biological Products/pharmacology , Cells, Cultured , Drug Synergism , HIV-1/physiology , Humans , T-Lymphocytes/drug effects , T-Lymphocytes/virology , Virus Replication/drug effects , Zidovudine/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Zeng-Sheng-Ping (ZSP), also called antitumor B, is a marketed Chinese traditional medicine used for cancer prevention. AIM OF THE STUDY: Currently, for the quality control of Chinese traditional medicines, marker compounds are not selected based on bioactivities and pharmaceutical behaviors in most of the cases. Therefore, even if the "quality" of the medicine is controlled, the pharmacological effect could still be inconsistent. The aim of this study is to establish an activity and absorption-based platform to select marker compound(s) for the quality control of Chinese traditional medicines. MATERIALS AND METHODS: We used ZSP as a reference Chinese traditional medicine to establish the platform. Activity guided fractionation approach was used to purify the major components from ZSP. NMR and MS spectra were used to elucidate the structure of the isolated compounds. MTT assay against oral carcinoma cell line (SCC2095) was performed to evaluate the activities. UPLC-MS/MS was used to quantify the pure compounds in ZSP and the active fraction. The permeabilities of the identified compounds were evaluated in the Caco-2 cell culture model. The intracellular accumulation of the isolated compounds was evaluated in the SCC2095 cells. RESULTS: The major compounds were identified from ZSP. The contents, anti-proliferation activities, permeabilities, and intracellular accumulations of these compounds were also evaluated. The structure of these purified compounds were identified by comparing the NMR and MS data with those of references as rutaevine (1), limonin (2), evodol (3), obacunone (4), fraxinellone (5), dictamnine (6), maackiain (7), trifolirhizin (8), and matrine (9). The IC50 of compounds 5, 6, and 7 against SCC2095 cells were significantly lower than that of ZSP. The uptake permeability of compounds 5, 6, and 7 were 2.58 ± 0.3 × 10(-5), 4.33 ± 0.5 × 10(-5), and 4.27 ± 0.8 × 10(-5) respectively in the Caco-2 cell culture model. The intracellular concentrations of these compounds showed that compounds 5, 6, and 7 were significantly accumulated inside the cells. CONCLUSION: Based on the activity against oral carcinoma cell line as well as the absorption permeability, compound 5, 6, and 7 are selected as quality control markers for ZSP. An activity and absorption-based platform was established and successfully used for the quality control of ZSP.
Subject(s)
Cell Proliferation/drug effects , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional/standards , Quality Control , Alkaloids/analysis , Alkaloids/isolation & purification , Benzofurans/analysis , Benzofurans/isolation & purification , Benzoxepins/analysis , Benzoxepins/isolation & purification , Cell Line, Tumor , Glucosides/analysis , Glucosides/isolation & purification , Glucosides/pharmacokinetics , Heterocyclic Compounds, 4 or More Rings/analysis , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Heterocyclic Compounds, 4 or More Rings/pharmacokinetics , Humans , Limonins/analysis , Limonins/isolation & purification , Permeability , Pterocarpans/analysis , Pterocarpans/isolation & purification , Pterocarpans/pharmacokinetics , Quinolines/analysis , Quinolines/isolation & purification , Quinolines/pharmacokinetics , Quinolizines/analysis , Quinolizines/isolation & purification , Triterpenes/analysis , Triterpenes/isolation & purification , MatrinesABSTRACT
Bioassay-guided isolation and fractionation of Berberis jaeschkeana Schneid var. jaeschkeana stem resulted in the isolation and characterisation of a new long chain hydroxy ester named as berberinol (1) along with six known compounds (2-7). All the structures were established from 1D and 2D spectroscopic data. Crude extract, sub-fractions and all the isolated compounds were evaluated for their anti-fungal and urease enzyme inhibition properties. All of the sub-fractions and compounds showed good anti-fungal and urease enzyme inhibition properties. Minimum inhibitory concentrations (MICs) were calculated for all active samples in case of urease enzyme inhibition. MICs values were found to be in the range of 39.03-49.78 µg/mL for urease enzyme inhibition.
Subject(s)
Antifungal Agents/isolation & purification , Berberis/chemistry , Plant Extracts/chemistry , Plant Stems/chemistry , Urease/antagonists & inhibitors , Antifungal Agents/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Esters/chemistry , Esters/isolation & purification , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Microbial Sensitivity Tests , Molecular StructureABSTRACT
Three new phenolic compounds (1-3) were isolated from the heartwood of Dalbergia odorifera T. Chen. (Leguminosae). Their structures were established based on spectroscopic methods including 1D and 2D NMR (HSQC, COSY, HMBC and ROESY). Compound 2 exhibited cytotoxicity against BEL-7402 tumor cell lines.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Benzofurans/isolation & purification , Chromones/isolation & purification , Dalbergia/chemistry , Drugs, Chinese Herbal/isolation & purification , Flavonoids/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Benzofurans/chemistry , Benzofurans/pharmacology , Chromones/chemistry , Chromones/pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Phenols/chemistryABSTRACT
A phytochemical study on Huperzia serrata led to the isolation of four new 5-deoxyfawcettimine-related Lycopodium alkaloids, huperserines A-D (1-4), and one new lycodine-type alkaloid, huperserine E (5). Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR techniques. 5-Carbonyl or 5-hydroxyl group is a typical characteristic of lycopodine- and fawcettimine-type alkaloids. This is the first report of the 5-deoxyfawcettimine type Lycopodium alkaloids. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that huperserine E exhibited moderate anti-AChE activity with an IC50 value of 6.71 µM.