Structural basis of binding and rationale for the potent urease inhibitory activity of biscoumarins.

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.

Hepatoprotection by chemical constituents of the marine brown alga Spatoglossum variabile: a relation to free radical scavenging potential.

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 β-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.

3-Formylchromones: potential antiinflammatory agents.

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.

1,3,4-Oxadiazole-2(3H)-thione and its analogues: a new class of non-competitive nucleotide pyrophosphatases/phosphodiesterases 1 inhibitors.

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.

Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus.

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.

Fungal transformation of dydrogesterone and inhibitory effect of its metabolites on the respiratory burst in human neutrophils.

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.

Inhibitory effect of lactone fractions and individual components from three species of the Achillea millefolium complex of Bulgarian origin on the human neutrophils respiratory burst activity.

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.

Ursolic acid: a potent inhibitor of superoxides produced in the cellular system.

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.

Microbial transformation of mesterolone.

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.

New biscoumarin derivatives-cytotoxicity and enzyme inhibitory activities.

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.

Inhibition of respiratory burst in human neutrophils and lipoxygenase enzyme by compounds from Haloxylon griffithii.

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.

Synthesis and anti-inflammatory activity of some selected aminothiophene analogs.

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).

Myocardial ischaemia and reperfusion injury: reactive oxygen species and the role of neutrophil.

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.

Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties.

The withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania somnifera, respectively, inhibited acetylcholinesterase (AChE, EC 3.1.1.

Bioactive phenolic compounds from a medicinal lichen, Usnea longissima.

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.

Juliflorine: a potent natural peripheral anionic-site-binding inhibitor of acetylcholinesterase with calcium-channel blocking potential, a leading candidate for Alzheimer's disease therapy.

The alkaloid juliflorine (1) from Prosopis juliflora inhibited acetylcholinesterase (AChE, EC 3.1.1.

Alkaloids of Aconitum laeve and their anti-inflammatory antioxidant and tyrosinase inhibition activities.

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.

Phenolic glyscosides, a new class of human recombinant nucleotide pyrophosphatase phosphodiesterase-1 inhibitors.

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.

In vitro anti-inflammatory effect of Carthamus lanatus L.

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.

Anti-inflammatory isoflavonoids from the rhizomes of Iris germanica.

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.