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1.
Biomed Res Int ; 2014: 935039, 2014.
Article in English | MEDLINE | ID: mdl-25295281

ABSTRACT

Urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and reactive cysteine residue in the active sites. In the current study we examined a series of biscoumarins 1-10 for their mechanisms of inhibition with the nickel containing active sites of Jack bean and Bacillus pasteurii ureases. All these compounds competitively inhibited Jack bean urease through interaction with the nickel metallocentre, as deduced from Michaelis-Menten kinetics, UV-visible absorbance spectroscopic, and molecular docking simulation studies. Some of the compounds behaved differently in case of Bacillus pasteurii urease. We conducted the enzyme kinetics, UV-visible spectroscopy, and molecular docking results in terms of the known protein structure of the enzyme. We also evaluated possible molecular interpretations for the site of biscoumarins binding and found that phenyl ring is the major active pharmacophore. The excellent in vitro potency and selectivity profile of the several compounds described combined with their nontoxicity against the human cells and plants suggest that these compounds may represent a viable lead series for the treatment of urease associated problems.


Subject(s)
Coumarins/chemistry , Urea/chemistry , Urease/chemistry , Bacillus/enzymology , Binding Sites , Canavalia/enzymology , Catalytic Domain , Coumarins/pharmacology , Cysteine/chemistry , Humans , Kinetics , Lewis Acids/chemistry , Molecular Docking Simulation , Nickel/chemistry , Protein Binding , Urea/metabolism , Urease/antagonists & inhibitors
2.
Pharm Biol ; 51(3): 383-90, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23406359

ABSTRACT

CONTEXT: In the course of searching hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine brown alga Spatoglossum variabile Figaro et DE Notar (Dictyoaceae) against CCl4-induced liver damage in Wistar rats was investigated. The compounds were first investigated for in vitro radical scavenging potential and were also tested for ß-glucuronidase inhibition to further explore the relationship between hepatoprotection and antiradical potential. METHODS: The compounds cinnamic acid esters 1 and 2 and aurone derivatives 3 and 4 were first investigated for in vitro radical scavenging potential against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and superoxide anion radicals. In vivo hepatoprotective studies were performed in seven groups (n = 6) of Wistar rats. The test groups were pretreated with compounds (10 mg/kg body weight, po) orally for 30 min before the intraperitoneal administration of a dose of 20% CCl4 diluted with dietary cooking oil. Moreover, compounds were also tested for ß-glucuronidase inhibition to explore the relationship between hepatoprotection and radical scavenging potential. RESULTS: The test compounds 1-4 were found to exhibit antiradical activity against 1,1-diphenyl-2-picrylhydrazyl radicals with IC50 values ranging between 54 and 138 µM, whereas aurone derivatives 3 and 4 additionally exhibited superoxide anion scavenging effects with IC50 values of 95 and 87 µM, respectively. In addition, these compounds were found to be weak inhibitors of xanthine oxidase (IC50 ≥1000 µM). In animal model, pretreatment with compounds 2-4 significantly blocked the CCl4-induced increase in the levels of the serum biochemical markers. CONCLUSION: It appears that the hepatoprotection afforded by these compounds was mainly due to their radical scavenging activity that protected the cells from the free radicals generated by CCl4-induced hepatotoxicity.


Subject(s)
Benzofurans/therapeutic use , Carbon Tetrachloride Poisoning/prevention & control , Cinnamates/therapeutic use , Free Radical Scavengers/therapeutic use , Liver/drug effects , Phaeophyceae/chemistry , Animals , Benzofurans/adverse effects , Benzofurans/chemistry , Benzofurans/pharmacology , Biomarkers/blood , Carbon Tetrachloride Poisoning/blood , Carbon Tetrachloride Poisoning/physiopathology , Cell Survival/drug effects , Cinnamates/adverse effects , Cinnamates/chemistry , Cinnamates/pharmacology , Drug Discovery , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Escherichia coli Proteins/antagonists & inhibitors , Free Radical Scavengers/adverse effects , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Glucuronidase/antagonists & inhibitors , Humans , Liver/physiopathology , Male , Milk Proteins/antagonists & inhibitors , Neutrophils/drug effects , Rats , Rats, Wistar , Xanthine Oxidase/antagonists & inhibitors
3.
Eur J Med Chem ; 45(9): 4058-64, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20576329

ABSTRACT

The synthesis and characterization of 3-formylchromone (1) and its derivatives 2-24 and evaluation of their potential antiinflammatory activities is reported here. These compounds were characterized by (1)H NMR, EI MS, IR, and UV spectroscopic techniques and elemental analysis. The synthesized compounds were evaluated by using various in vitro and in vivo assay models for antiinflammatory activity and their effects were compared with known standard drug such as aspirin and indomethacin. Among all tested compounds, 1, 2, 5, 6, 9, 14, 16-19, 21-23, showed promising antiinflammatory activities. The results and SAR has been discussed in this report.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chromones/chemistry , Chromones/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Carrageenan/pharmacology , Chromones/chemical synthesis , Chromones/therapeutic use , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/chemistry , Cyclooxygenase Inhibitors/pharmacology , Cyclooxygenase Inhibitors/therapeutic use , Edema/chemically induced , Edema/drug therapy , Female , Inflammation/drug therapy , Male , Prostaglandin-Endoperoxide Synthases/metabolism , Rats , Rats, Wistar , Respiratory Burst/drug effects , Xanthine/metabolism , Xanthine Oxidase/metabolism
4.
Bioorg Med Chem ; 17(22): 7816-22, 2009 Nov 15.
Article in English | MEDLINE | ID: mdl-19822431

ABSTRACT

A series of 1,3,4-oxadiazole-2 (3H)-thiones and 1,3,4-thiadiazole-2 (3H)-thiones were synthesized and evaluated for their inhibitory activities against the two nucleotide pyrophosphatase phosphodiesterase 1 enzymes. Dixon, as well as Lineweaver-Burk plots, and their secondary replots have indicated that the inhibition was of pure non-competitive type, against both snake venom and pure human recombinant enzymes as the V(max) values decreases without affecting the K(m) values. 5-[4-(t-Butyldimethylsilyloxy)-phenyl]-1,3,4-thiadiazole-2 (3H)-thione (17) and [4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2 (3H)-thione (1) were found to be the most active compounds with IC(50) values 66.47 and 368microM, respectively. The K(i) values were 100microM and 360microM against the snake venom and human recombinant NPP1 enzyme, respectively. Most active compounds were found to be non-toxic in neutrophil viability assay.


Subject(s)
Enzyme Inhibitors/pharmacology , Oxadiazoles/pharmacology , Phosphodiesterase I/antagonists & inhibitors , Pyrophosphatases/antagonists & inhibitors , Thiadiazoles/pharmacology , Thiones/pharmacology , Cell Line , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/metabolism , Humans , Inhibitory Concentration 50 , Kinetics , Neutrophils/drug effects , Neutrophils/enzymology , Oxadiazoles/chemical synthesis , Oxadiazoles/metabolism , Phosphodiesterase I/metabolism , Pyrophosphatases/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Thiadiazoles/chemical synthesis , Thiadiazoles/chemistry , Thiones/chemical synthesis , Thiones/metabolism
5.
Phytother Res ; 23(9): 1336-9, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19173281

ABSTRACT

Several secondary metabolites, artemetin (1), casticin (2), 3,3'-dihydroxy-5,6,7,4'-tetramethoxy flavon (3), penduletin (4), methyl 4-hydroxybenzoate (5), p-hydroxybenzoic acid (6), methyl 3,4-dihydroxybenzoate (7), 5-hydroxy-2-methoxybenzoic acid (8), vanillic acid (9) and 3,4-dihydroxybenzoic acid (10) were isolated from a folkloric medicinal plant, Vitex agnus-castus. The structures of compounds 1-10 were identified with the help of spectroscopic techniques. Compounds 3-10 were isolated for the first time from this plant. These compounds were screened for their antiinflammatory and lipoxygenase inhibitory activities. Compounds 6, 7 and 10 were found to have significant antiinflammatory activity in a cell-based contemporary assay, whereas compounds 1 and 2 exhibited a potent lipoxygenase inhibition.


Subject(s)
Anti-Inflammatory Agents/isolation & purification , Lipoxygenase Inhibitors/isolation & purification , Plant Extracts/pharmacology , Vitex/chemistry , Anti-Inflammatory Agents/pharmacology , Cells, Cultured , Flavonoids/isolation & purification , Flavonoids/pharmacology , Humans , Inhibitory Concentration 50 , Lipoxygenase Inhibitors/pharmacology , Molecular Structure , Neutrophils/drug effects
6.
Chem Biodivers ; 5(2): 324-31, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18293446

ABSTRACT

The biotransformation of the synthetic hormone dydrogesterone (1) by a number of fungal strains - including Cephalosporium aphidicola, Rhizopus stolonifer, Cunninghamella elegans, and Fusarium lini - afforded ten different metabolites, compounds 2-11. From a structural point of view, these transformations involved a combination of hydroxylation, oxidation, reduction, and/or epoxidation. The pregnane-based metabolites 10 and 11 are new compounds. All the known compounds were obtained for the first time from 1 by fungal transformation. The metabolites 3, 5, and 8 showed more-potent respiratory-burst inhibitory activity than the substrate 1 in a neutrophil-based cellular assay (Table 3).


Subject(s)
Dydrogesterone/metabolism , Mitosporic Fungi/metabolism , Mucorales/metabolism , Neutrophils/drug effects , Pregnanes/metabolism , Respiratory Burst/drug effects , Biotransformation , Dydrogesterone/chemistry , Humans , Molecular Conformation , Neutrophils/metabolism , Pregnanes/chemistry , Pregnanes/pharmacology , Stereoisomerism , Structure-Activity Relationship
7.
Nat Prod Res ; 21(11): 1032-6, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17691054

ABSTRACT

Achillea species are widely used in folk medicine for treatment of inflammatory diseases. The inhibitory effect on the human neutrophils respiratory burst activity of total extracts, their fractions and some main constituents of the flower heads from Achillea asplenifolia, A. collina and A. distans belonging to A. millefolium complex of Bulgarian origin, were tested by the modified method of Tan and Berridge. Seven from the investigated fractions showed activity similar or higher than that of indomethacine and might be evaluated as nonsteroidal anti-inflammatory agents.


Subject(s)
Achillea/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Lactones/isolation & purification , Lactones/pharmacology , Neutrophils/drug effects , Plants, Medicinal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Bulgaria , Humans , Indomethacin/pharmacokinetics , Indomethacin/pharmacology , Lactones/chemistry , Medicine, Traditional , Respiratory Burst
8.
Phytother Res ; 21(6): 558-61, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17295383

ABSTRACT

Triterpenoids of ursane class: ursolic acid, ilelatifol D, corosolic acid and euscaphic acid were isolated for the first time from Leonurus cardiaca, a member of the family Lamiaceae. The isolated compounds were tested for their cell-based antiinflammatory potential by suppressing respiratory burst activity and superoxide scavenging property by using xanthine/xanthine oxidase system to produce superoxides in the cell-free system. Ursolic acid was found to be an excellent inhibitor for the superoxides produced in the cellular system, while the same was inactive in the superoxide scavenging activity in cell-free system.


Subject(s)
Free Radical Scavengers/pharmacology , Respiratory Burst/drug effects , Superoxides/antagonists & inhibitors , Triterpenes/pharmacology , Cells, Cultured , Dose-Response Relationship, Drug , Free Radical Scavengers/chemistry , Humans , Lamiaceae/chemistry , Molecular Structure , Neutrophils/cytology , Neutrophils/drug effects , Neutrophils/metabolism , Superoxides/metabolism , Triterpenes/chemistry , Xanthine Oxidase/metabolism , Ursolic Acid
9.
Bioorg Med Chem ; 14(23): 8066-72, 2006 Dec 01.
Article in English | MEDLINE | ID: mdl-16919464

ABSTRACT

Biscoumarin derivatives 1-27 were tested for their inhibition of snake venom and human nucleotide pyrophosphatase phosphodiesterase-1 enzymes. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds are pure non-competitive inhibitors of both the enzymes. Ki and IC50 values of biscoumarins were found to be in the range of 50 to 1000 and 164 to > 1000 microM, respectively, against human recombinant phosphodiesterase 1 enzyme and 8.0 to 1150 and 9.44 to > 1000 microM, respectively, against snake venom phosphodiesterase. Compounds 1, 3, 4, 6, 7, 17, 26, and 30 were found to be non-competitive and non-cytotoxic upto a concentration of 200 microg/mL as evident by less than 10% cell death after 3 h of incubation.


Subject(s)
Coumarins/pharmacology , Enzyme Inhibitors/chemical synthesis , Phosphodiesterase I/antagonists & inhibitors , Pyrophosphatases/antagonists & inhibitors , Cell Death/drug effects , Coumarins/chemical synthesis , Drug Evaluation, Preclinical , Enzyme Inhibitors/pharmacology , Humans , Inhibitory Concentration 50 , Kinetics , Phosphoric Diester Hydrolases , Snake Venoms/enzymology
10.
Phytother Res ; 20(10): 840-3, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16835879

ABSTRACT

Secondary metabolites, ferulic acid (1), 2,6-dimethoxy-4-hydroxy acetophenone (2), herniarin (3), p-hydroxy acetophenone (4), methyl 3,4-dihydroxycinnamate (5), and methyl 4-hydroxy-3-methoxycinnamate (6) were isolated from Haloxylon griffithii, a member of the family Chenopodiaceae. The structures of compounds 1-6 were identified with the help of spectroscopic techniques. These compounds were isolated for the first time from this plant. The lipoxygenase and respiratory burst inhibitory activities were determined. Compound 5 was found to be the most potent inhibitory activity against respiratory burst in human neutrophils among all the compounds as well as exhibited moderate lipoxygenase inhibitory activity from this plant.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chenopodiaceae/chemistry , Lipoxygenase Inhibitors/pharmacology , Neutrophils/drug effects , Respiratory Burst/drug effects , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cells, Cultured , Humans , Lipoxygenase Inhibitors/chemistry , Lipoxygenase Inhibitors/isolation & purification , Neutrophils/physiology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology
11.
J Enzyme Inhib Med Chem ; 21(2): 139-43, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16789427

ABSTRACT

Some 2-aminothiophene analogs 1-6 were synthesized and characterized. Among the tested compounds, compound 1 (IC50 121.47 microM) exhibited highest while the compound 5 showed least anti-inflammatory potential (IC50 422 microM).


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Thiophenes/chemical synthesis , Thiophenes/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Drug Design , Humans , Inhibitory Concentration 50 , Neutrophils/drug effects , Neutrophils/metabolism , Thiophenes/chemistry
12.
J Coll Physicians Surg Pak ; 15(8): 507-14, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16202368

ABSTRACT

A growing body of evidence suggests that oxygen radicals can mediate myocardial tissue injury during ischaemia and, in particular, during reperfusion. This review focuses on the role of neutrophil as a mediator of myocardial damage. Upon reperfusion, neutrophils accumulate and produce an inflammatory response in the myocardium that is responsible, in part, for the extension of tissue injury associated with reperfusion. It has shown that the inhibition of neutrophil accumulation and adhesion is associated with decreased infarct size. This strongly suggests that myocardial cells at risk region undergo irreversible changes upon reperfusion and accumulation of neutrophils. Several pharmacological agents (ibuprofen, allopurinol, prostacyclin, and prostaglandin E analogues) protect the myocardium from reperfusion injury. In addition, the mechanisms by which these agents act and directions of research that may lead to therapeutically useful approaches are also discussed in this review.


Subject(s)
Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/physiopathology , Neutrophils/physiology , Allopurinol/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Epoprostenol/pharmacology , Free Radical Scavengers/pharmacology , Humans , Ibuprofen/pharmacology , Iloprost/pharmacology , Myocardial Reperfusion Injury/prevention & control , Prostaglandins E, Synthetic/pharmacology , Reactive Oxygen Species/pharmacology
13.
Phytochemistry ; 66(19): 2346-50, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16102789

ABSTRACT

Natural products, longissiminone A (1) and longissiminone B (2), were isolated along with a known compound, glutinol (3), from a medicinal lichen, Usnea longissima. The structures of compounds 1 and 2 were determined with the help of spectroscopic studies. Compound 1 was found to possess potent anti-inflammatory activity in a cell-based contemporary assay. Cytotoxicity activity measured by cell viability assay showed 100% viability in the presence of 200 microg/mL conc. of these compounds.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Benzene Derivatives/isolation & purification , Triterpenes/isolation & purification , Usnea/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Benzene Derivatives/chemistry , Benzene Derivatives/pharmacology , Benzene Derivatives/toxicity , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Molecular Structure , Neutrophils/drug effects , Triterpenes/chemistry , Triterpenes/pharmacology , Triterpenes/toxicity
14.
Biochem Biophys Res Commun ; 334(1): 276-87, 2005 Aug 19.
Article in English | MEDLINE | ID: mdl-16108094

ABSTRACT

The withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania somnifera, respectively, inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent fashion with IC50 values ranging between 20.5 and 49,2 microm and 29.0 and 85.2 microm for AChE and BChE, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that compounds 1, 3, and 5 are the linear mixed-type inhibitors of AChE, while 2 and 4 are non-competitive inhibitors of AChE with K(i) values ranging between 20.0 and 45.0 microm. All compounds were found to be non-competitive inhibitors of BChE with K(i) values ranging between 27.7 and 90.6 microm. Molecular docking study revealed that all the ligands are completely buried inside the aromatic gorge of AChE, while compounds 1, 3, and 5 extend up to the catalytic triad. A comparison of the docking results showed that all ligands generally adopt the same binding mode and lie parallel to the surface of the gorge. The superposition of the docked structures demonstrated that the non-flexible skeleton of the ligands always penetrates the aromatic gorge through the six-membered ring A, allowing their simultaneous interaction with more than one subsite of the active center. The affinity of ligands with AChE was found to be the cumulative effects of number of hydrophobic contacts and hydrogen bonding. Furthermore, all compounds also displayed dose-dependent (0.005-1.0 mg/mL) spasmolytic and Ca2+ antagonistic potentials in isolated rabbit jejunum preparations, compound 4 being the most active with an ED50 value of 0.09 +/- 0.001 mg/mL and 0.22 +/- 0.01 microg/mL on spontaneous and K+ -induced contractions, respectively. The cholinesterase inhibitory potential along with calcium antagonistic ability and safe profile in human neutrophil viability assay could make compounds 1-5 possible drug candidates for further study to treat Alzheimer's disease and associated problems.


Subject(s)
Acetylcholinesterase/chemistry , Calcium/metabolism , Ergosterol/chemistry , Ergosterol/toxicity , Jejunum/metabolism , Models, Chemical , Models, Molecular , Neutrophils/drug effects , Animals , Calcium Signaling/drug effects , Cell Survival/drug effects , Cells, Cultured , Cholinesterase Inhibitors/analysis , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/toxicity , Computer Simulation , Dose-Response Relationship, Drug , Ergosterol/analogs & derivatives , Humans , Jejunum/drug effects , Lethal Dose 50 , Models, Biological , Molecular Conformation , Neutrophils/pathology , Rabbits , Withania/metabolism
15.
Biochem Biophys Res Commun ; 332(4): 1171-7, 2005 Jul 15.
Article in English | MEDLINE | ID: mdl-16021692

ABSTRACT

The alkaloid juliflorine (1) from Prosopis juliflora inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent fashion with IC50 values 0.42 and 0.12 microM, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that the nature of inhibition was purely of non-competitive type with Ki values 0.4 and 0.1 microM, against AChE and BChE, respectively. By molecular docking studies compound 1 was found to be ideally spaced inside the aromatic gorge of AChE with rings A/B remaining at the top and rings C/D penetrating deep into the gorge, that might be due to the greater hydrophobicity of rings C/D as compared to rings A/B, allowing their simultaneous interaction with the peripheral anionic and quaternary ammonium-binding sites. The 1-AChE complex was found to be stabilized by hydrophobic contacts, hydrogen bonding, and pi-pi stacking between the compound 1 and amino acid residues of the aromatic gorge of AChE. Amino acid residues Tyr70, Asp72, Tyr121, Trp279, and Tyr334 of the peripheral anionic site (PAS) of AChE were found to be exclusively involved in the hydrophobic contacts with compound 1 that might be responsible for the competitive mode of inhibition. Compound 1 also showed dose-dependent (30-500 microg/mL) spasmolytic and Ca2+-channel blocking activities in isolated rabbit jejunum preparations. The cholinesterase inhibitory potential along with calcium-channel blocking activity of compound 1 and safe profile in human neutrophils viable assay could make it a possible drug candidate for Alzheimer's disease.


Subject(s)
Alkaloids/pharmacology , Alzheimer Disease/drug therapy , Calcium Channels/metabolism , Cholinesterase Inhibitors/pharmacology , Animals , Binding Sites , Calcium/metabolism , Cholinesterase Inhibitors/chemistry , Dose-Response Relationship, Drug , Humans , Hydrogen Bonding , Inhibitory Concentration 50 , Kinetics , Models, Chemical , Models, Molecular , Molecular Conformation , Neutrophils/metabolism , Protein Binding , Protein Conformation , Torpedo , Tyrosine/chemistry
16.
Phytochemistry ; 66(8): 935-40, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15934134

ABSTRACT

A lycoctonine-type norditerpenoid alkaloid, swatinine (1), along with four known norditerpenoid alkaloids, delphatine (3), lappaconitine (4), puberanine (5), and N-acetylsepaconitine (6), and were isolated from the aerial parts of Aconitum laeve Royle. Compound 2 has been isolated for the first time from a natural source. The structure of compound 1 was deduced on the basis of spectral data. The anti-inflammatory, antioxidant and tyrosinase inhibition studies on all six compounds have also been carried out.


Subject(s)
Aconitum/chemistry , Alkaloids/chemistry , Alkaloids/pharmacology , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Monophenol Monooxygenase/antagonists & inhibitors , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Free Radicals , Humans , In Vitro Techniques , Models, Molecular , Molecular Structure , Plant Components, Aerial/chemistry
17.
Chem Biodivers ; 2(3): 392-400, 2005 Mar.
Article in English | MEDLINE | ID: mdl-17191988

ABSTRACT

The microbial transformation of mesterolone (= (1alpha,5alpha,17beta)-17-hydroxy-1-methylandrostan-3-one; 1), by a number of fungi yielded (1alpha,5alpha)-1-methylandrostane-3,17-dione (2), (1alpha,3beta,5alpha,17beta)-1-methylandrostane-3,17-diol (3), (5alpha)-1-methylandrost-1-ene-3,17-dione (4), (1alpha,5alpha,15alpha)-15-hydroxy-1-methylandrostane-3,17-dione (5), (1alpha,5alpha,6alpha,17beta)-6,17-dihydroxy-1-methylandrostan-3-one (6), (1alpha,5alpha,7alpha,17beta)-7,17-dihydroxy-1-methylandrostan-3-one (7), (1alpha,5alpha,11alpha,17beta)-11,17-dihydroxy-1-methylandrostan-3-one (8), (1alpha,5alpha,15alpha, 17beta)15,17-dihydroxy-1-methylandrostan-3-one (9), and (5alpha,15alpha,17beta)-15,17-dihydroxy-1-methylandrost-1-en-3-one (10). Metabolites 5-10 were found to be new compounds. All metabolites, except 2, 3, 6, and 7, exhibited potent anti-inflammatory activity. The structures of these metabolites were characterized on the basis of spectroscopic studies, and the structure of 5 was also determined by single-crystal X-ray-diffraction analysis.


Subject(s)
Fungi/metabolism , Mesterolone/pharmacokinetics , Biotransformation , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mesterolone/chemistry , Species Specificity
18.
Bioorg Med Chem ; 12(22): 5793-8, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15558843

ABSTRACT

Cytotoxicity and kinetic studies of phenolic glycosides, benzoyl salireposide (1) and salireposide (2), isolated from Symplocos racemosa, were performed against phosphodiesterase I enzyme from snake venom and human nucleotide pyrophosphatase phosphodiesterase-1. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds are pure non-competitive inhibitors of both enzymes. K(i) Values of compounds 1 and 2 were found to be 360 and 1000 microM, respectively, against human nucleotide pyrophosphatase phosphodiesterase, and 525 and 1100 microM, respectively, against snake venom phosphodiesterase. IC(50) values of compounds 1 and 2 are 90 microM +/- 0.04 and 383 microM +/- 0.03, respectively, against human nucleotide pyrophosphatase phosphodiesterase and 171 microM +/- 0.02 and 544 microM +/- 0.021, respectively, against snake venom phosphodiesterase. Both compounds were found to be nontoxic up to concentration of 500 microM/mL as >90% cells were viable after 3 h of incubation. These compounds are potential candidates for the therapy of arthritis.


Subject(s)
Glycosides/chemistry , Phenols/chemistry , Protease Inhibitors/chemistry , Pyrophosphatases/antagonists & inhibitors , Animals , Glycosides/metabolism , Humans , Phenols/metabolism , Phosphodiesterase I/antagonists & inhibitors , Phosphodiesterase I/metabolism , Phosphoric Diester Hydrolases/metabolism , Protease Inhibitors/metabolism , Pyrophosphatases/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism
19.
J Ethnopharmacol ; 86(2-3): 177-80, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12738083

ABSTRACT

The anti-inflammatory activity of nine isoflavonoids 5,7-dihydroxy-3-(3'-hydroxy-4',5'dimethoxy)-8-methoxy-4H-1-benzopyran-4-one 1, 5,7-dihydroxy-3-(3'-hydroxyl-4', 5'-dimethoxy)-6-methoxy-4H-1-benzopyran-4-one 2, 5, 7-dihydroxy-3-(4'-hydroxy)-6-methoxy-4H-1-benzopyrane-4-one 3, 5-hydroxy-3-(4'-hydroxy)-6,7-methylenedioxy-4H-1-benzopyran-4-one 4, 5-hydroxy-3-(4'-methoxy)-6,7-methylenedioxy-4H-1-benzopyran-4-one 5, 5-methoxy-3-(4'-hydroxy)-6,7-methyenedioxy-4H-1-benzopyran-4-one 6, 5,7-dihydroxy-3-(3'-hydroxy-4'-methoxy)-6-methoxy-4H-1-benzopyran-4-one 7, 5,7-dihydroxy-3-(3'-methoxy-4'-hydroxy)-6-methoxy-4H-1-benzopyran-4-one 8, and isopeonol 9 determined by a spectrophotometric assay using the activated human neutrophils. These isoflavonoids were isolated from an important folkloric medicinal plant Irsa (Iris germanica L.), a member of the family Iridaceae. Structures of these compounds were identified by spectral comparison with the reported data and active members of this group adds into the growing number of non-steroidal anti-inflammatory agents.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Iris Plant , Isoflavones , Medicine, Traditional , Plant Preparations , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Humans , Isoflavones/chemistry , Isoflavones/isolation & purification , Isoflavones/pharmacology , Neutrophils/drug effects , Plant Preparations/chemistry , Plant Preparations/isolation & purification , Plant Preparations/pharmacology , Rhizome , Spectrophotometry , Structure-Activity Relationship
20.
Z Naturforsch C J Biosci ; 58(11-12): 830-2, 2003.
Article in English | MEDLINE | ID: mdl-14713160

ABSTRACT

The anti-inflammatory activity of four total extracts, their fractions and two main constituents (alpha-bisabolol beta-D-fucopyranoside and luteolin 7-O-glucoside) of Carthamus lanatus L. aerial parts, were assessed in vitro by determining the inhibitory effects on induced human neutrophils. The dichloromethane extract and its water-alcoholic part exhibited the most significant inhibitory effects.


Subject(s)
Anti-Inflammatory Agents/chemistry , Carthamus/chemistry , Neutrophils/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Neutrophils/physiology , Plant Components, Aerial/chemistry , Solvents
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