Wnt/ß-catenin signaling plays an important role in the protective effects of FDP-Sr against oxidative stress induced apoptosis in MC3T3-E1 cell.

Strontium fructose 1,6-diphosphate (FDP-Sr) is a new strontium-containing compound. The primary aim of this study was to clarify whether the structure component of FDP-Sr, FDP could benefit the protective effect of Sr (II) against oxidative stress induced apoptosis, and meanwhile to further explore the important role of Wnt/ß-catenin signaling in the anti-apoptosis effect of FDP-Sr in response to oxidative stress induced by H2O2 in an osteoblastic MC3T3-E1 cell line. Results showed that FDP-Sr could improve the osteoblastic differentiation under oxidative stress with induced cell proliferation and improved mineralization. The inhibition effect of FDP-Sr on cell apoptosis induced by H2O2 was proved by reduced reactive oxygen species production and activated caspase3. Under oxidative stress, mRNA and protein levels of phospho-ß-catenin reduced, while ß-catenin increased in the FDP-Sr treatment cell, leaded to the up-regulations of Runx2 and OPG at both mRNA and protein levels, finally improved the differentiation of osteoblasts. By the engagement of Wnt/ß-catenin pathway's inhibitor (XAV-939), the protective effects of FDP-Sr on osteoblastic differentiation against oxidative stress were repressed along with inhibited wnt/ß-catenin signaling and reduced mRNA and protein levels of Runx2 and OPG. In conclusion, FDP-Sr was demonstrated to protect osteoblast differentiation from oxidative damage induced by H2O2 through up-regulation of Wnt/ß-catenin signaling, and FDP in FDP-Sr was able to directly improve the oxidative stress injury through its ROS scavenging ability.

2-(1-Methyl-2-oxoindolin-3-yl-idene)malono-nitrile.

The title mol-ecule, C12H7N3O, is almost planar, with an r.m.s. deviation of 0.026 Å. No directional interactions could be detected in the crystal.

5-Methyl-N-(1,3-thia-zol-2-yl)isoxazole-4-carboxamide.

In the title compound, C8H7N3O2S, the dihedral angle between the thia-zol and isoxazole rings is 34.08 (13)°. In the crystal, the mol-ecules are linked by pairs of N-H⋯N hydrogen bonds, forming inversion dimers, and C-H⋯O inter-actions, resulting in chains along the b-axis direction.

rac-Methyl 2-(2-formyl-4-nitro-phen-oxy)hexa-noate.

In the racemic title compound, C(14)H(17)NO(6), the plane of the ester group of the methyl hexa-noate side chain makes a dihedral angle of 80.0 (2)° with the benzene ring, while the nitro group is approximately coplanar with the benzene ring [dihedral angle = 10.3 (2)°]. In the crystal, mol-ecules form weak aromatic C-H⋯O(nitro) hydrogen-bonding inter-actions, giving inversion dimers [graph set R(2) (2)(8)].

5-Methyl-N-[2-(trifluoro-meth-yl)phen-yl]isoxazole-4-carboxamide.

In the title compound, C(12)H(9)F(3)N(2)O(2), the benzene ring is nearly perpendicular to the isoxazole ring, making a dihedral angle of 82.97 (2)°. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into a supra-molecular chain running along the c axis.

[2-(1H-Indol-4-yl)eth-yl]dipropyl-amine.

In the title compound, C(16)H(24)N(2), the aliphatic amine substituent is rotated almost orthogonally [C-C-C-C torsion angle = 75.7 (3)°] out of the plane of the indole unit. The amine N atom has a pyramidal configuration deviating by 0.380 (3) Šfrom the plane of the adjacent C atoms. All of the aliphatic groups are in extended transoid conformations. In the crystal, mol-ecules form chains along the a axis via N-H⋯N hydrogen bonds.

N-Cyclo-hexyl-N-{[3-(4,6-dimeth-oxy-pyrimidin-2-yl-oxy)pyridin-2-yl]meth-yl}4,6-dimeth-oxy-pyrimidin-2-amine.

In the title compound, C(24)H(30)N(6)O(5), the cyclo-hexyl ring adopts a chair conformation, while the remainder of the mol-ecule adopts a U-shape. The dihedral angles between the pyridine ring and the pendant pyrimidine rings are 69.04 (12) and 75.99 (9)°. The two pyrimidine rings, however, are nearly parallel to one another, with a dihedral angle of 8.56 (15)° between them. They are also involved in an intra-molecular π-π stacking inter-action with a distance of 3.6627 (18) Šbetween the ring centroids. In the crystal, C-H⋯O contacts link the mol-ecules into chains along the b axis.

2-(Hy-droxy-meth-yl)pyridin-3-ol.

In the crystal structure of the title compound, C(6)H(7)NO(2), the mol-ecules are are linked by inter-molecular O-H⋯N and O-H⋯O hydrogen bonds; π-π stacking is observed between parallel pyridine rings of adjacent mol-ecules [centroid-to-centroid distance = 3.7649 (12) Å].

2-[(4,6-Dimeth-oxy-pyrimidin-2-yl)-oxy]benzaldehyde.

In the title compound, C(13)H(12)N(2)O(4), the dihedral angle between the benzene and pyrimidine rings is 55.57 (13)°. The carbonyl group and the two methoxyl groups are approximately coplanar with the benzene ring and pyrimidine ring; the C-C-C-O, C-O-C-N and C-O-C-C torsion angles being -6.1 (5), -4.8 (4) and 179.9 (3)°, respectively. In the crystal, mol-ecules are linked via C-H⋯O inter-actions, forming chains propagating along [110].

6-Chloro-1-methyl-indoline-2,3-dione.

The title mol-ecule, C(9)H(6)ClNO(2), is essentially planar: the maximum deviation from the mean plane of the indoline ring is 0.020 (2) Šand the substituents do not deviate by more than 0.053 (2) Šfrom this plane. C-H⋯O hydrogen bonds help to consolidate the crystal structure.

1-Benzyl-4-chloro-indoline-2,3-dione.

There are two independent mol-ecules in the asymmetric unit of the title compound, C(15)H(10)ClNO(2), which differ in the dihedral angles between the mean planes of the phenyl ring and the 4-chloro-indoline-2,3-dione ring system [59.48 (9) and 79.0 (1)°]. In the crystal, mol-ecules are linked through C-H⋯O hydrogen bonds, forming polymeric chains in [100].

N-(4-Chloro-2-nitro-phen-yl)-5-methyl-isoxazole-4-carboxamide.

In the title compound, C(11)H(8)ClN(3)O(4), the dihedral angle between benzene and isoxazole rings is 9.92 (1) °. The nitro group is almost coplanar with the benzene ring with an O-N-C-C torsion angle of 8.4 (3)°. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond, closing a six-membered ring.

1-Benzyl-6-chloro-indoline-2,3-dione.

In the title compound, C(15)H(10)ClNO(2),the dihedral angle between the mean planes of the benzene and 6-chloro-indoline-2,3-dione ring systems, linked through a methyl-ene group, is 81.68 (10)°. In the crystal, mol-ecules are connected by C-H⋯O hydrogen bonds, generating C(6) chains propagating in [010].

Study on bioavailability difference between clopidogrel bisulfate form I and form II using liquid chromatography/tandem mass spectrometry.

The bioavailability of clopidogrel bisulfate (CAS 135046-48-9) form I was compared with that of clopidogrel bisulfate form II in 12 male Sprague-Dawley rats. The rats, randomly divided into two groups, received a single oral dose of 8 mg/kg clopidogrel (CP) bisulfate form I and form II, respectively, under fasting condition. The plasma concentrations of CP and its inactive carboxylic acid metabolite (CAS 144457-28-3, IM) were simultaneously determined by a sensitive, specific LC-MS/MS method. The pharmacokinetic parameters included C(max), T(max), t1/2, AUC(0-t), AUC(0-infinity). The AUC(0-infinity) of CP was 13.78 +/- 0.67 and 11.46 +/- 1.98 ng/ mL x h for CP form I and form II, respectively. The AUC(0-infinity) of IM was 33.08 +/- 5.76 and 21.67 +/- 8.95 microg/mL x h for CP form I and form II, respectively. The maximum plasma concentration (C(max)) of CP was 3.81 +/- 0.54 ng/mL for CP form I and 3.18 +/- 0.31 ng/mL for CP form II, the C(max) of IM was 3.42 +/- 0.41 and 2.08 +/- 0.68 microg/ mL for the CP form I and form II, respectively. There was an obvious difference between form I and form II for C(max) and the area under the plasma concentration time curve for both CP and IM after a t-test. This study shows that CP form I has better bioavailability in rats than CP form II.

6-(1H-Tetra-zol-5-yl)-1H-indole monohydrate.

In the title compound, C(9)H(7)N(5)·H(2)O, the tetra-zole ring forms a dihedral angle of 1.82 (1)° with the mean plane of the indole fragment. In the crystal, mol-ecules are linked by inter-molecular O-H⋯N, N-H⋯O and N-H⋯N hydrogen bonds into a two-dimensional network parallel to (100). Addtional stabilization is provide by weak π-π inter-actions with a centroid-centroid distance of 3.698 (2) Å.

3-Chloro-azepan-2-one.

In the title compound, C(6)H(10)ClNO, an inter-mediate for the production of lysine, there are intra-molecular C-H⋯Cl hydrogen bonds.

4-(1H-Tetra-zol-5-yl)-1H-indole.

There are two mol-ecules with similar configurations in the asymmetric unit of the title compound, C(9)H(7)N(5), which are linked by inter-molecular N-H⋯N hydrogen bonds into chains with graph-set motif C(2) (2)(8) along the b axis. The indole core has the expected planar geometry in the two mol-ecules, with a maximum deviation of 0.008 (8) Šfrom the least-squares plane defined by the nine constituent atoms, and the dihedral angles between the indole and tetra-zole rings are similar [42.4 (2) and 42.7 (2)°].

1-Benzoyl-3-chloro-azepan-2-one.

In the crystal structure of the title compound, C(13)H(14)ClNO(2), inter-molecular C-H⋯O inter-actions link the mol-ecules into a two-dimensional network.