M. P. Sadashiva

A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis

Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimers disease, cardiovascular diseases (CVDs) and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.

5-(Prop-2-yn-1-yl)-5H-dibenzo[b,f]azepine: ortho-rhom-bic polymorph.

In the title orthorhombic polymorph (space group Iba2), C17H13N, the dihedral angle between the benzene rings is 55.99 (10)° and the azepine ring adopts a boat conformation. In the crystal, molecules are linked by C—H⋯π contacts. The previously-reported polymorph [Yousuf et al. (2012 ▶). Acta Cryst. E68, o1101] crystallizes in the monoclinic system (space group P21/c) with two molecules in the asymmetric unit.

5-[(4-Benzyl-1H-1,2,3-triazol-1-yl)meth­yl]-5H-dibenzo[b,f]azepine

In the title compound, C24H20N4, the azepine ring adopts a boat conformation and the dihedral angle between the benzene rings fused to it is 57.95 (8)°. The bond-angle sum at the azepine N atom is 346.6°, indicating a significant deviation from planarity. The triazole ring subtends a dihedral angle of 71.45 (10)° with the terminal phenyl group. A weak intramolecular C—H⋯Na (a = azepine) interaction occurs, which closes an S(6) ring.

Synthesis, Characterization, Crystal Structure, and Hirshfeld Surface Analysis of (2Z)-3-(methylsulfanyl)-2,3-diphenylprop 2-enenitrile

The title compound, C16H13NS (3) was synthesized and characterized by 1H nuclear magnetic resonance (NMR), mass spectra (MS), infrared (IR), thermogravimetric analysis, differential scanning calorimeter (DSC) and finally the structure is confirmed by single crystal X-ray diffraction method. The compound 3 crystallizes in the monoclinic crystal system and space group C2/c, with crystal parameters, a = 10.99364(4) Å, b = 12.3517(3) Å, c = 20.1045(6) Å, β = 103.082(3)0, Z = 8, and V = 2647.30(14) Å3. The structure of the compound reveals that the intermolecular interactions of the type C–H…π, C– H…N, and S…S. The packing diagram of the molecules in the unit cell exhibit three-dimensional architecture. In addition inter contacts involved in intermolecular interactions are quantified using Hirshfeld surfaces analysis.

Crystal Structure, Spectral Studies, and Hirshfeld Surfaces Analysis of 5-Methyl-5H-dibenzo[b,f]azepine and 5-(4-Methylbenzyl)-5H-dibenzo[b,f]azepine

The compounds, 5-methyl-5H-dibenzo[b,f]azepine (1) and 5-(4-methylbenzyl)-5H-dibenzo[b,f]azepine (2), were synthesized and characterized by spectral studies, and finally confirmed by single crystal X-ray diffraction method. The compound 1 crystallizes in the orthorhombic crystal system in Pca21 space group, having cell parameters (18) A, (18) A, (13) A, and and (3) A3. And the compound 2 crystallizes in the orthorhombic crystal system and space group Pbca, with cell parameters (5) A, (2) A, (7) A, and and (16) A3. The azepine ring of both molecules 1 and 2 adopts boat conformation with nitrogen atom showing maximum deviations of 0.483 (2) A and 0.5025 (10) A, respectively. The C–H⋯π short contacts were observed. The dihedral angle between fused benzene rings to the azepine motif is 47.1 (2)° for compound 1 and 52.59 (6)° for compound 2, respectively. The short contacts were analyzed and Hirshfeld surfaces computational method for both molecules revealed that the major contribution is from C⋯H and H⋯H intercontacts.

5-[(1-Benzyl-1H-1,2,3-triazol-4-yl)meth­yl]-5H-dibenzo[b,f]azepine

In the title compound, C24H20N4, the azepine ring adopts a boat conformation. The dihedral angle between the benzene rings fused to the azepine ring is 49.40 (9)°. The triazole ring makes a dihedral angle of 77.88 (9)° with the terminal phenyl ring. In the crystal, molecules are linked via C—H⋯π interactions and a parallel slipped π–π interaction [centroid–centroid distance = 3.7324 (9), normal distance = 3.4060 (6) and slippage = 1.526 Å], forming a three-dimensional network.

Crystal structure of 2-(4-chloro­phen­yl)-3-(4-meth­oxy­phen­yl)-3-(methyl­sulfanyl)­acrylo­nitrile

In the title compound, C17H14ClNOS, the aromatic rings are inclined to one another by 64.22 (9)°. The acrylonitrile group (C=C—C N) is planar to within 0.003 (2) Å, with the S atom and the methyl C atom displaced from this plane by 0.2317 (6) and −0.637 (2) Å, respectively. In the crystal, molecules are linked via pairs of C—H⋯π interactions, forming inversion dimers. There are no other significant intermolecular interactions present.

Crystal structure of 5-(1-benzo-furan-2-yl)-3-(4-methyl-phen-yl)-4,5-di-hydro-1,2-oxazol-5-ol.

In the title compound, C18H15NO3, the isoxazole moiety adopts a shallow envelope conformation, with the C atom bearing the OH group displaced by 0.148 (1) Å from the mean plane through the other four atoms. The mean plane of this ring (all atoms) subtends dihedral angles of 87.19 (6) and 15.51 (7)° with the benzofuran ring system (r.m.s. deviation = 0.007 Å) and the 4-methylphenyl ring, respectively. In the crystal, molecules are linked by O—H⋯N hydrogen bonds, generating [001] C(5) chains, with adjacent molecules in the chain related by c-glide symmetry. Weak C—H⋯O interactions link the chains into a three-dimensional network.

A triclinic polymorph of (E)-2-(4-iso­butyl­phen­yl)-N′-[1-(4-nitro­phen­yl)ethyl­idene]propano­hydrazide

The asymmetric unit of the triclinic polymorph of the title compound, C21H25N3O3, consists of two molecules, whereas for the monoclinic polymorph Z′ = 1 [Fun et al. (2009 ▶). Acta Cryst. E65, o445]. The two molecules exhibit an E configuration with respect to the C=N bond. The molecules are linked into dimers by N—H⋯O and C—H⋯O hydrogen bonds forming R 2 2(8) ring motifs. In addition, π–π interactions occur between nitrophenyl groups [minimum centroid–centroid distance 3.940 (2) Å], stacking the molecules along the ac plane.

4-[5-(4-Benzoyl-oxyphen-yl)-1,2,4-oxa-diazol-3-yl]phenyl benzoate.

In the title compound, C28H18N2O5, the dihedral angle between the terminal benzoate rings is 20.67 (12)°. The central oxadiazole ring is almost coplanar with its two benzene ring substituents, making dihedral angles of 4.80 (16) and 5.82 (16)°. In the crystal, pairs of C—H⋯O hydrogen bonds form inversion dimers with R 2 2(40) ring motifs. The structure also features C—H⋯O, C—H⋯π and π–π interactions [centroid–centroid separation = 3.695 (4) Å].