Synthesis, in vitro and computational studies of 1,4-disubstituted 1,2,3-triazoles as potential α-glucosidase inhibitors.

1,4-Disubstituted-1,2,3-triazoles were synthesized by Cu(I) catalyzed click reaction, where the azides, with electron donating and electron withdrawing groups acted as 1,3-dipoles and 1-ethynyl-1-cyclohexanol served as the terminal alkyne. These synthesized triazoles were subjected to enzymatic assay which showed promising activity against α-glucosidase; 1-(2-cyano-4-nitrophenyl)-4-(1-hydroxycyclohexyl)-1H-1,2,3-triazole 3m being the most active members of the library. Molecular docking studies of these triazoles with the homology-modeled α-glucosidase protein were also performed to delineate ligand-protein interactions at molecular level which suggested that Phe157, Arg312 and His279 are the major interacting residues in the biding site of the protein and may have a significant role in the inhibition of enzyme's function.

Biologically active bergenin derivatives from Bergenia stracheyi.

New bergenin derivatives, bergecins A and B (1 and 2, resp.), have been isolated from the AcOEt-soluble fraction of Bergenia stracheyi, along with bergenin (3), and their structures were elucidated on the basis of (1) H- and (13) C-NMR spectra, and by COSY, HMQC, and HMBC experiments. Compound 2 showed potent inhibitory potential against the enzyme lipoxygenase, while 1 was moderately active. On the other hand, both compounds exhibited significant antioxidant activities in 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay.

New aromatic esters from Galinsoga parviflora.

Galinosoates A-C (1-3), new aromatic esters, have been isolated from the n-hexane soluble fraction of Galinsoga parviflora. Their structures were assigned from the spectral data including IR, HR-EI-MS, 1D and 2D NMR.

Bioactive phenolic amides from Celtis africana.

Nine compounds have been isolated for the first time from Celtis africana, namely trans-N-coumaroyltyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), lauric acid (4), oleic acid (5), palmitic acid (6), lupeol (7), ß-sitosterol (8) and oleanolic acid (9), respectively. Their structures have been elucidated by different spectroscopic techniques. The isolated compounds were screened for their antioxidant, anti-inflammatory and acetylcholinestrease enzyme inhibitory activities. Compounds 1-3 showed significant antioxidant and anti-inflammatory activities and weak to moderate acetylcholinestrease enzyme inhibition activity.

{5-Chloro-2-[(4-chloro-benzyl-idene)-amino]-phen-yl}(phen-yl)methanone.

In the title compound, C(20)H(13)Cl(2)NO, the C=N bond adopts an E conformation. The chloro-substituted rings form a dihedral angle of 11.99 (9)° with each other and form dihedral angles of 74.95 (9) and 83.26 (10)° with the unsubstituted ring. In the crystal, mol-ecules are connected into dimers by pairs of weak C-H⋯O hydrogen bonds and the dimers are arranged in columns parallel to the a axis.

N'-[(Z)-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)methyl-idene]-2-hy-droxy-benzohydrazide.

In the title compound, C(19)H(18)N(4)O(3), the pyrazole ring is oriented at dihedral angles of 41.12 (7) and 12.25 (10)°, respectively, with respect to the planes of the phenyl and benzene rings. Intra-molecular N-H⋯O and O-H⋯O hydrogen bonds generate seven- and six-membered S(7) and S(6) ring motifs, respectively.

[4,4'-(Ethane-1,2-diyldinitrilo)-bis-(pent-2-en-2-olato)]copper(II) 0.25-hydrate.

In the title compound, [Cu(C(12)H(18)N(2)O(2))]·0.25H(2)O, the coordination of the O,N,N',O'-tetra-dentate ligand results in a cis-CuN(2)O(2) square-planar geometry for the metal ion and the presence of two six-membered and one five-membered chelate rings. The complete complex mol-ecule is close to planar (r.m.s. deviation = 0.047 Å). The uncoordinated water mol-ecule (O-atom site symmetry 2) was modelled as half occupied. In the crystal, C-H⋯O(w) and O(w)-H⋯O (w = water) hydrogen bonds link the components into layers parallel to ab plane.

Evaluation of antioxidant and urease inhibition activities of roots of Glycyrrhiza glabra.

The object of this study is to determine the antioxidant activity of extracts from Glycyrrhiza glabra roots. The parent extract is methanolic extract while its sub fractions were prepared in ethyl acetate, chloroform, and n-butanol. The method based on scavenging activity and reduction capability of 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH). Urease inhibition activities of these extracts were also evaluated. Chloroform fraction was the most effective antioxidant with 87.7% activity but the activity is less than the crude methanolic extract i.e. 90%. Chloroform fraction showed the same trend in reducing power as that in radical scavenging activity. However n- butanol extract was devoid of any activity when compared to standard BHA. Crude methanolic fraction and its sub-fractions were also screened for enzyme inhibition activities using jackbean urease as substrate. Significant anti urease activity i.e. 72 % was observed in the ethyl acetate fraction with respect to standard inhibitor thiourea.

Sorbicins A and B, new urease and serine protease inhibitory triterpenes from Sorbus cashmiriana.

Two new lupene-type triterpenes, sorbicins A and B, have been isolated from the chloroform-soluble fraction of the MeOH extract from the whole plant of Sorbus cashmiriana, and their structures were elucidated by spectroscopic techniques including 2D NMR. Both compounds displayed urease and α-chymotrypsin inhibitory potential.

Antioxidant and urease inhibitory C-glycosylflavonoids from Celtis africana.

Two new C-glycosylflavonoids celtisides A (1) and B (2) have been isolated from n-butanol-soluble fraction of Celtis africana, along with five known C-glycosylflavonoids vitexin (3), orientin (4), isoswertiajaponin (5), isoswertisin (6), and 2″-O-rhamnosyl vitexin (7) reported for the first time from this species. Their structures were assigned from 1D and 2D NMR spectra. These compounds were investigated for biological activities and showed significant antioxidant and urease inhibitory activities.

In vitro antituberculosis activities of the constituents isolated from Haloxylon salicornicum.

In vitro antituberculosis activities of fractions and pure compounds (1-20) including seven triterpenes, two alkaloids, two cycloheximide derivatives, two coumarins six sterol derivatives and a long chain alcohol, respectively, isolated from Haloxylon salicornicum were determined against Mycobacterium tuberculosis H37Rv. Actively growing cultures were tested by rapid colorimetric method while the stationary phase cultures were tested by drug exposure methods for bactericidal activity. The MIC values were found to be 50 microg/ml for compounds 15, 19 and 20 where as rest of the compounds invariably showed MIC value of 100 microg/ml against the logarithmic phase culture. These were compare to Isoniazid as a control drug. The compounds exhibited no activity against the stationary phase culture of M. tuberculosis H37Rv up to 200 microg/ml. Further studies are required to investigate the in vivo efficacies and activities of the compounds in combination with antimicrobials that are already being used for TB therapy.

Conferin, potent antioxidant and anti-inflammatory isoflavone from Caragana conferta Benth.

Conferin (1), a new isoflavone, has been isolated from the ethyl acetate soluble fraction of Caragana conferta Benth. along with seven known compounds, namely biochanin A (2), p-hydroxybenzoic acid (3), 3,5-dimethoxybenzoic acid (4), ursolic acid (5), erythrodiol (6), pinoresinol (7), and syringresinol (8), reported for the first time from this species. The structure of the new isoflavone was deduced on the basis of spectroscopic studies. Compounds 1 and 2 were investigated for biological activities and showed significant anti-inflammatory activity in carrageenan induced paw edema of rats. Evaluation of antioxidant activity by the radical scavenging method indicated that compound 1 is a potent antioxidant while 2 is moderately active. It was also shown that the reducing capability of compound 2 was remarkably increased in a concentration dependent manner as compared to 1. Compound 1 showed moderate inhibitory activity against the enzyme lipoxygenase, while 2 showed weak activity.

{2-[(Benzo-yloxy)meth-yl]-1-oxo-3H-pyrrolizin-2-yl}methyl benzoate.

The title compound, C(23)H(19)NO(5), was prepared by esterification of 2,2-bis-(hy-droxy-meth-yl)-2,3-dihydro-1H-pyrrolizin-1-one with benzoyl chloride in pyridine·The pyrrolizine ring system is approximately planar with a maximum deviation of 0.008 (2) Šfrom the least-squares plane; the two phenyl rings are oriented at dihedral angles of 64.26 (11) and 70.75 (10)° with respect to the pyrrolizine ring system. Weak inter-molecular C-H⋯O hydrogen bonding occurs in the crystal structure.

3-Phenyl-1H-pyrrolo[2,1-c][1,4]oxazin-1-one.

The mol-ecule of the title compound, C(13)H(9)NO(2), is slightly twisted with a dihedral angle of 4.85 (9)° between the nine-membered ring system and the phenyl ring. The nine non-H atoms of the 1H-pyrrolo[2,1-c][1,4]oxazin-1-one system are coplanar [r.m.s. deviation = 0.0122 (2) Å]. In the crystal, weak inter-molecular C-H⋯O inter-actions link mol-ecules into chains along [10]. The crystal studied was an inversion twin with a 0.48624 (9):0.51376 (9) domain ratio.

2,2-Bis(hy-droxy-meth-yl)-2,3-dihydro-1H-pyrrolizin-1-one.

The title compound, C(9)H(11)NO(3), was prepared by an Aldol reaction of 2,3-dihydro-1H-pyrrolizin-1-one with formaldehyde. The asymmetric unit contains six mol-ecules. The pyrrolizine ring system in each mol-ecule is planar, the maximum atomic deviation being 0.066 (2) Å. In the crystal structure, mol-ecules are liked together by an extensive O-H⋯O hydrogen-bonding network.

N-[2-(3-Methyl-1-oxo-1,2-dihydro-pyrrolo-[1,2-a]pyrazin-2-yl)eth-yl]methane-sulfonamide.

In the title compound, C(11)H(15)N(3)O(3)S, the dihedral angle between the five- and six-membered rings is 1.13 (18)°. The ethyl-methane-sulfonamide group is in a (+)synclinal conformation. In the crystal, inter-molecular N-H⋯O and C-H⋯O hydrogen-bond inter-actions link mol-ecules into zigzag ribbons parallel to the b axis. The ribbons are further connected by C-H⋯π inter-actions.

Xanthine oxidase/tyrosinase inhibiting, antioxidant, and antifungal oxindole alkaloids from Isatis costata.

Phytochemical investigations on the ethyl acetate soluble fraction of the whole plant of Isatis costata Linn. (Brassicaseae) led to the isolation of the oxindole alkaloids costinones A (1), B (2), isatinones A (3), B (4), indirubin (5), and trisindoline (6). Compounds 1-6 displayed significant to moderate inhibition against xanthine oxidase enzyme with IC50 values ranging from 90.3+/-0.06 to 179.6+/-0.04 microM, whereas the standard inhibitor of xanthine oxidase (allopurinol) had an IC(50) value of 7.4+/-0.07 microM. Compounds 1 (IC50 7.21+/-0.05 microM), 2 (IC50 9.40+/-0.03 microM), 3 (IC50 11.51+/-0.07 microM), 4 (IC50 12.53+/-0.06 microM), 5 (IC50 14.29+/-0.09 microM), and 6 (IC50 17.34+/-0.04 microM) exhibited pronounced activities when compared with the standard tyrosinase inhibitor L-mimosine (IC50 3.70+/-0.03 microM), along with DPPH radical scavenging activity with IC50 226, 270, 300, 320, 401, and 431 microM, respectively. The crude extract and compounds 1, 2, 5, and 6 showed significant antifungal activity against Trichophyton schoen leinii, Aspergillus niger, Candida albicans, Trichophyton simii, and Macrophomina phaseolina.

Galinsosides A and B, bioactive flavanone glucosides from Galinsoga parviflora.

Galinsosides A (1) and B (2), new flavanone glucosides together with two known flavanones, 7,3',4'-trihydroxyflavanone (3) and 3,5,7,3',4'-pentahydroxyflavanone (4) have been isolated from an ethyl acetate- soluble fraction of Galinsoga parviflora. Their structures were assigned on the basis of spectral studies. Compound 1 showed significant antioxidant and urease inhibitory activity while compound 2 was moderately active. On the other hand, 2 showed inhibitory potential against alpha-glucosidase.

Asphorodin, a potent lipoxygenase inhibitory triterpene diglycoside from Asphodelus tenuifolius.

Asphorodin (1), a new diglycoside, has been isolated from the ethyl acetate-soluble fraction of Asphodelus tenuifolius. It showed significant inhibitory activity against the enzyme lipoxygenase in a concentration-dependent manner. The Lineweaver-Burk and Dixon plots indicated that the nature of inhibition was non-competitive.

Antioxidant constituents from Cotoneaster racemiflora.

A new lignan rhamnoside, racemiside (1), has been isolated from the ethyl acetate-soluble fraction of Cotoneaster racemiflora, along with scopoletin (2), 7,8-dimethoxy-6-hydroxycoumarin (3), 3,3',4'-tri-O-methylellagic acid (4), and cereotagloperoxide (5), reported for the first time from this species. All of them showed profound antioxidative activities in the DPPH assay.