Synthesis of (4R)-thiazolidine carboxylic acid and evaluation of antioxidant potential.

We report here the synthesis as well as antioxidant activity of a series of 2-aryl thiazolidine-4-carboxylic acids, including two novel derivatives. They were synthesized by nucleophilic cyclic condensation of L-cysteine hydrochloride with a range of aromatic aldehydes. Their in vitro antioxidant activity was evaluated by DPPH radical scavenging assay. It was observed that the aromatic substituent at C-2 of thiazolidine ring effects the antioxidant potential of the thiazolidine derivatives. The nature and position of the substituents on aromatic ring were correlated with antioxidant activity. Compounds with -OCH3 group on aromatic ring showed a better radical scavenging property than the other groups such as -Cl, -F, and -NO2. The presence of phenyl ring thus enhanced radical scavenging activity.

Combination Therapy of Clinically Approved Antifungal Drugs Is Enhanced by Conjugation with Silver Nanoparticles.

Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90-100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 µg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.

Novel fluorene-based supramolecular sensor for selective detection of amoxicillin in water and blood.

Synthesis, characterization and molecular recognition properties of fluorene based supramolecular cleft 1 is reported. The cleft molecule 1 was prepared in a single-step with good yield (85% yield), by linking Fluorene with 1-ethyl piperazine. The cleft molecule 1 was carefully characterized using various spectroscopic techniques such as NMR and mass spectrometry. The supramolecular interaction of cleft 1 with amoxicillin, 6APA, aspirin, captopril, cefotaxime, ceftriaxone, cefuroxime, diclofenac, penicillin, and cephradine was evaluated by fluorescent spectroscopy. The molecular recognition studies showed that amoxicillin selectively binds with cleft 1 in the presence of other drugs. The analytical method developed for the supramolecular interaction of molecular cleft 1 and amoxicillin was validated at varying pH, concentration and temperature during recognition process. Job's plots indicated that the stochiometry of the interactions between the cleft 1 and the amoxicillin was 1:1.

Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure-activity relationships.

Context Dodonaea viscosa (L.) Jacq (Sapindaceae) has been used in traditional medicine as antimalarial, antidiabetic and antibacterial agent, but further investigations are needed. Objective This study determines the antioxidant and anticholinesterase activities of six compounds (1-6) and two crystals (1A and 3A) isolated from D. viscosa, and discusses their structure-activity relationships. Materials and methods Antioxidant activity was evaluated using six complementary tests, i.e., ß-carotene-linoleic acid; DPPH(•), ABTS(•+), superoxide scavenging, CUPRAC and metal chelating assays. Anticholinesterase activity was performed using the Elman method. Results Clerodane diterpenoids (1 and 2) and phenolics (3-6) - together with three crystals (1A, 3A and 7A) - were isolated from the aerial parts of D. viscosa. Compound 3A exhibited good antioxidant activity in DPPH (IC50: 27.44 ± 1.06 µM), superoxide (28.18 ± 1.35% inhibition at 100 µM) and CUPRAC (A0.5: 35.89 ± 0.09 µM) assays. Compound 5 (IC50: 11.02 ± 0.02 µM) indicated best activity in ABTS assay, and 6 (IC50: 14.30 ± 0.18 µM) in ß-carotene-linoleic acid assay. Compounds 1 and 3 were also obtained in the crystal (1A and 3A) form. Both crystals showed antioxidant activity. Furthermore, crystal 3A was more active than 3 in all activity tests. Phenol 6 possessed moderate anticholinesterase activity against acetylcholinesterase and butyrylcholinesterase enzymes (IC50 values: 158.14 ± 1.65 and 111.60 ± 1.28 µM, respectively). Discussion and conclusion This is the first report on antioxidant and anticholinesterase activities of compounds 1, 2, 5, 6, 1A and 3A, and characterisation of 7A using XRD. Furthermore, the structure-activity relationships are also discussed in detail for the first time.

Urease inhibitory constituents from Daphne retusa.

The bioassay-guided fractionation of Daphne retusa Hemsl. has led to the isolation of a new aryl tetrahydronaphthalene lignan derivative named as daphnretusic acid (1), along with six new source compounds such as 5,7-dihydroxyflavone (2), 7-hydroxyflavone (3), 6-methoxyflavone (4), (+) pinoresinol (5), (+) sesamin (6), and ß-sitosterol-3-O-ß-D-glucopyranoside (7). Their structures were elucidated by (1)H NMR, (13)C NMR, 1D, 2D NMR, UV, IR, and EIMS analyses. All the fractions (n-hexane, CHCl3, AcOEt, CH3OH, and water) and pure compounds (1-7) were subjected to the assay of urease and α-chymotrypsin inhibitory activities. Chloroform and methanol soluble fractions showed moderate urease inhibition. Compound 2 exhibited significant urease inhibition with IC50 value 60.4 ± 0.72 µM, whereas compounds 1 and 3-7 remained inactive during urease inhibition and α-chymotrypsin bioassays.

Methylenebissantin: a rare methylene-bridged bisflavonoid from Dodonaea viscosa which inhibits Plasmodium falciparum enoyl-ACP reductase.

A new methylene-bridged bisflavonoid, methylenebissantin (1), and nine known compounds, including flavonoids (2-5), diterpenoids (6 and 7), and phenol derivatives (8-10) were isolated from the aerial parts of Dodonaea viscosa Jacq. The structure elucidation was based on spectroscopic data analyses. The isolated compounds were evaluated for the inhibition of Plasmodium falciparum enoyl-ACP reductase (PfENR). Methylenebissantin (1) exhibited a moderate inhibition (IC(50) 91.13 µM) against PfENR.

{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.

[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.

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.

Anti-inflammatory xanthones from the twigs of Hypericum oblongifolium wall.

Two new xanthonolignoids, hypericorin A (1) and hypericorin B (2), along with five known new source compounds, a xanthonolignoid, kielcorin (3), 4-hydroxy-2,3-dimethoxyxanthone (4), 3,4,5-trihydroxyxanthone (5), 1,3-dihydroxy-5-methoxyxanthone ( 6) and 1,3,7-trihydroxyxanthone (7), were isolated from the stems (twigs) of Hypericum oblongifolium Wall. The structures of the new compounds were deduced on the basis of spectroscopic techniques (EI-MS, HREI-MS, (1)H NMR, (13)C NMR, HMQC, HMBC, and NOESY). We also report herein for the first time the single crystal X-ray structure of compound 6. Compounds 1- 7 were screened for their IN VITRO anti-inflammatory (respiratory burst) inhibiting activities using isolated human neutrophils; compounds 1, 2, 3, 5, and 7 showed significant activities (IC (50) = 816.23 ± 73.30, 985.20 ± 55.80, 965.21 ± 65.80, 907.20 ± 50.80, 975.20 ± 81.10 µM, respectively), compound 6 showed moderate activity (IC (50) = 2500.85 ± 50.50 µM), while compound 4 was totally inactive at 1000 µg/mL as compared to the positive control used, indomethacin (IC (50) = 757.99 ± 5.90 µM), and aspirin (IC (50) = 279.44 ± 4.40 µM). Compound 4 was also inactive in comparison with other tested Hypericum compounds.

Dimethyl 2,2'-({2,2'-methyl-enebis[6-(2H-benzotriazol-2-yl)-4-(2,4,4-trimethyl-pentan-2-yl)-2,1-phenyl-ene]}di-oxy)diacetate.

The asymmetric unit of the title compound, C(47)H(58)N(6)O(6), comprises three independent mol-ecules, in one of which one tert-butyl group is disordered in a 1:1 ratio. The mol-ecule is a di(ar-yl)methane having two aliphatic and one N-heterocyclic substituent in each aryl ring. For the mol-ecule having the disordered tert-butyl group, the aryl rings make an angle of 115.3 (2)° at the methyl-ene carbon; one aryl ring is aligned at 42.0 (1)° with respect to the N-heterocyclic substituent and the other at 48.7 (1)° with respect to its substituent. The two ordered mol-ecules are disposed about a pseudo center of inversion. The pairs of twist angles in these two mol-ecules differ [52.7 (1) and 61.7 (1)°, and 29.1 (1) and 58.5 (1)°].

Bis[3-(2H-benzotriazol-2-yl)-2-(prop-2-yn-yloxy)-5-(2,4,4-trimethyl-pentan-2-yl)phen-yl]methane.

In the title compound, C(47)H(54)N(6)O(2), the C-C-C bond angle between the rings is 108.40 (13)°. One aryl ring aligned at 38.5 (1)° with respect to the N-heterocyclic substituent and the other at 56.0 (1)° with respect to its substituent. In the crystal, adjacent mol-ecules are linked by C-H⋯N hydrogen bonds, forming a chain extending along the a axis.

Bis[5-chloro-2-(prop-2-yn-1-yl-oxy)phen-yl]methane.

The mol-ecule of the title compound, C(19)H(14)Cl(2)O(2), has two benzene rings connected to a methyl-ene C atom, and the rings are aligned at 66.3 (1)°. Inter-molecular C-H⋯π and π-π stacking inter-actions are observed in the crystal structure, the centroid-centroid distances between parallel benzene rings being 3.7529 (12) and 3.6201 (12) Å, respectively.

2,3-Dimeth-oxy-benzaldehyde azine.

There are one-and-a-half independent mol-ecules in the asymmetric unit of the title compound, C(18)H(20)N(2)O(4). One mol-ecule is centrosymmetric with the mid-point of the N-N bond located on a center of inversion. In the other, which lies on a general position, the benzene rings are aligned at 21.6 (1)°. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal strcture.

Di-tert-Butyl 2,2'-[2,2'-methyl-enebis(naphthalene-2,1-diyldi-oxy)]diacetate.

In the title compound, C(33)H(36)O(6), two naphthalene ring systems are connected through a methyl-ene linkage [C-C-C = 114.9 (2)°]; the ring systems are aligned at an angle of 76.5 (1)°. Of the two -O-CH(2)-C(=O)-C(CH(3))(3) substituents, one adopts an extended conformation whereas the other is U-shaped. In the crystal, mol-ecules are linked via weak C-H⋯O hydrogen bonding, forming supra-molecular chains running along the c axis.

tert-Butyl 2-(4-nitro-phen-oxy)acetate.

In the title mol-ecule, C(12)H(15)NO(5), the nitro-phen-oxy portion is approximately planar (r.m.s. deviation = 0.034 Å) and makes an angle of 84.8 (1)° with respect to the -CH(2)-C(=O)-O-C fragment. In the crystal, π-π stacking is observed between nearly parallel benzene rings of adjacent mol-ecules, the centroid-centroid distance being 3.6806 (10) Å. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

Urease inhibitors from Hypericum oblongifolium WALL.

The bioassay-guided fractionation of H. oblongifolium has led to the isolation of potent urease inhibitors 1-3. The structures were elucidated by NMR and mass spectroscopic techniques. Compound 2 showed a potent enzyme inhibition activity (IC(50) 20.96 +/- 0.93), which is comparatively higher than that for the standard thiourea (IC(50) 21.01 +/- 0.51 microM). Compounds 1 and 3 also showed a significant activity, with IC(50) 37.95 +/- 1.93 and 138.43 +/- 1.23 microM, respectively. The sub crude fractions (F1, F2, F3, and F4) were tested in vitro for their urease inhibition activity. Fractions F2 and F4 showed significant activity with IC(50) 140.37 +/- 1.93 and 167.43 +/- 3.03 microM, respectively.

2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl 2-nitro-benzoate.

In the title compound, C(13)H(12)N(4)O(6), the mean plane through the nitro-benzene forms a dihedral angle of 37.38 (15)° with the plane through the imidazole ring. The crystal packing is stabilized by weak inter-molecular C-H⋯O and C-H⋯N inter-actions together with π-π stacking inter-actions between nitro-benzene rings [centroid-centroid distance = 3.788 (3) Å] and between imidazole rings [centroid-centroid distance = 3.590 (2) Å].

6,7-Dihydro-3H-1,4-diazepino[1,2,3,4-lmn][1,10]phenanthroline-3,9(5H)-dione.

In the title compound, C(15)H(12)N(2)O(2), the seven-membered ring bearing the three methyl-ene C atoms displays a puckered conformation, with the methyl-ene C atoms deviating from the plane of the benzene ring by 0.05 (1), 0.98 (1) and 1.04 (1) Å. The phenanthroline unit is not planar; the dihedral angles between this benzene ring and the other pyridyl rings are 9.62 (4) and 9.31 (4)°. The crystal packing is stabilized by π-π inter-actions between two phenanthroline ring systems, forming a centrosymmetric dimer with a centroid-centroid distance of 3.656 (1) Å.

Diethyl 2,2'-(biphenyl-2,2'-diyldi-oxy)diacetate.

In the title compound, C(20)H(22)O(6), the mean planes through the benzene rings make a dihedral angle of 59.82 (7)° with each other. Weak inter-molecular C-H⋯O inter-actions together with π-π stacking inter-actions [centroid-centroid distance = 3.830 (1) Å] between benzene rings are observed in the crystal packing.