In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids.

A new series of pyrazole, phenylpyrazole, and pyrazoline analogs of diarylpentanoids (excluding compounds 3a, 4a, 5a, and 5b) was pan-assay interference compounds-filtered and synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. Each analog was evaluated for its anti-inflammatory ability via the suppression of nitric oxide (NO) on IFN-γ/LPS-activated RAW264.7 macrophage cells. The compounds were also investigated for their inhibitory capability toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), using a modification of Ellman's spectrophotometric method. The most potent NO inhibitor was found to be phenylpyrazole analog 4c, followed by 4e, when compared with curcumin. In contrast, pyrazole 3a and pyrazoline 5a were found to be the most selective and effective BChE inhibitors over AChE. The data collected from the single-crystal X-ray diffraction analysis of compound 5a were then applied in a docking simulation to determine the potential binding interactions that were responsible for the anti-BChE activity. The results obtained signify the potential of these pyrazole and pyrazoline scaffolds to be developed as therapeutic agents against inflammatory conditions and Alzheimer's disease.

3,4-Dimethoxybenzohydrazide derivatives as antiulcer: Molecular modeling and density functional studies.

3,4-Dimethoxybenzohydrazide derivatives (1-25) have been synthesized and evaluated for their urease inhibitory potential. Among the series, compounds 2, 3, 4 and 5 with IC50 values 12.61 ±â€¯0.07, 18.24 ±â€¯0.14, 19.22 ±â€¯0.21, and 8.40 ±â€¯0.05 µM, respectively, showed excellent urease inhibitory potentials when compared with standard thiourea (IC50 value 21.40 ±â€¯0.21 µM). Compounds 1, 6, 8, 18, 19 and 20 also showed good to moderate inhibition, while the remaining compounds were found to be completely inactive. The structures of compounds 6 and 25 were confirmed through X-ray crystallography while the structures of remaining compounds were confirmed through ESI-MS and 1H NMR. Molecular docking studies were performed understand the binding interactions with enzyme active site. The synthesized compounds were evaluated for cytotoxicity and found to be nontoxic.

Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines.

The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01µM and 8c, IC50=4.86µM) and U937 (8b, IC50=3.44µM and 8c, IC50=1.65µM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78µM and 15b, IC50=1.9µM while U937: 15a, IC50=0.95µM and 15b, IC50=0.92µM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-ß, ERK, JNK2, p38α and p38ß were performed using the conformation of 15a determined by single-crystal XRD.

Inhibition of prostaglandin E(2) production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation.

The discovery of potent inhibitors of prostaglandin E2 (PGE2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a vast array of biological signals and physiological events that contributes to inflammatory diseases such as rheumatoid arthritis, atherosclerosis, cancer, and pain. In this Letter, we report the synthesis of a series of minor prenylated chalcones and flavonoids which was found to be significantly active in suppressing the PGE2 production secreted by lipopolysaccharide-induced mouse macrophage cells (RAW 264.7). Among the compounds tested, 14b showed a dose-response inhibition of PGE2 production with an IC50 value of 2.1 µM. The suppression upon PGE2 secretion was not due to cell death since 14b did not reduce the cell viability in close proximity to the PGE2 inhibition concentration. The obtained atomic coordinates for the single-crystal XRD of 14b was then applied in the docking simulation to determine the potential important binding interactions with murine COX-2 and mPGES-1 putative binding sites.

2,4-Di-chloro-N-[eth-yl(2-hy-droxy-eth-yl)carbamo-thio-yl]benzamide.

In the title compound, C12H14Cl2N2O2S, the mol-ecule adopts a cis conformation with respect to the di-chloro-benzoyl group against the thiono group about the C-N bond. However, the di-chloro-benzene group and the thio-urea moiety are twisted by 75.41 (8)°. An intra-molecular N-H⋯O hydrogen bond occurs between the amido H atom and hydroxyl O atom. In the crystal, O-H⋯S and O-H⋯O hydrogen bonds link the molecules, forming chains along the b-axis direction.

4,4'-({[(Pyridine-2,6-di-yl)bis-(methyl-ene)]bis-(-oxy)}bis-(methyl-ene))dibenzo-nitrile.

The complete title molecule, C23H19N3O2, is generated by a twofold axis passing through the central ring. The two oxymethyl-benzo-nitrile arms are attached at the meta positions of the central pyridine ring. The dihedral angle between the pyridine ring and benzene ring of both arms is 84.55 (6)° while the benzene rings make a dihedral angle of 46.07 (7)°. In the crystal, weak C-H⋯π inter-actions link the molecules sheets parallel to the ac plane.

Crystal structure of 4-cyclo-hexyl-1-(propan-2-yl-idene)thio-semicarbazide.

In the title compound, C10H19N3S, the cyclo-hexyl group adopts a chair conformation and adopts a position approximately syn to the thione S atom. The CN2S thio-urea moiety makes dihedral angle of 13.13 (10)° with the propan-2-yl-idene-amino group. An intra-molecular N-H⋯N hydrogen bond is noted. In the crystal, inversion dimers linked by pairs of N-H⋯S hydrogen bonds generate R (2) 2(8) loops.

N-(2-Chloro-5-nitro-phen-yl)-N'-(3-chloro-propion-yl)thio-urea.

The title compound, C10H9Cl2N3O3S, adopts a trans-cis conformation with respect to the position of chloropropionyl and chloronitrobenzene groups respectively, against the thiono about their C-N bonds. The conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond. In the crystal, there is a short Cl⋯Cl contact with a distance of 3.386 (13) Å.

1-(4-Chloro-butano-yl)-3-(3-chloro-phen-yl)thio-urea.

The two independent mol-ecules in the asymmetric unit of the title compound, C11H12Cl2N2OS, exhibit different conformations, with the benzene ring and the N2CS thio-urea group forming dihedral angles of 87.40 (18) and 69.42 (15)°. An intra-molecular N-H⋯O hydrogen bond is present in each mol-ecule. Two further N-H⋯O hydrogen bonds link the independent mol-ecules into a dimer. In the crystal, the dimers are linked by N-H⋯S and C-H⋯S hydrogen bonds, forming chains parallel to the c axis.

1-(4-Bromo-phen-yl)-3-(3-chloro-propan-oyl)thio-urea.

The title compound, C10H10BrClN2OS, adopts a trans-cis conformation with respect to the position of the 3-chloro-propanoyl and 4-bromo-phenyl groups, respectively, against the thiono C=S bond across their C-N bonds. The benzene ring makes a dihedral angle of 9.55 (16)° with the N2CS thio-urea moiety. Intra-molecular N-H⋯O and C-H⋯S hydrogen bonds occur. In the crystal, mol-ecules are linked into chains along the c-axis direction by N-H⋯S, C-H⋯S and C-H⋯O hydrogen bonds.

3-[3-(2-Fluoro-benzo-yl)thio-ureido]propionic acid.

In the title compound, C10H11FN3O3S, the 2-fluoro-benzoyl and proponic acid groups maintain a trans-cis conformation with respect to the thiono C=S bond across their C-N bonds. The propionic acid group adopts an anti conformation about the C-C bond, with an N-C-C-C torsion angle of 173.8 (2)°. The amino groups are involved in the formation of intra-molecular N-H⋯O and N-H⋯F hydrogen bonds. In the crystal, pairs of O-H⋯O hydrogen bonds link mol-ecules into inversion dimers.

Crystal structure of (E)-N'-benzyl-idene-2-meth-oxy-benzohydrazide.

In the title benzoyl-hydrazide derivative, C15H14N2O2, the dihedral angle between the planes of the two phenyl rings is 12.56 (9)°. The azomethine double bond adopts an E configuration stabilized by an N-H⋯O hydrogen bond. In the crystal, the components are linked by C-H⋯O inter-actions to form chains along the b axis.

Crystal structure of 4-fluoro-N-[2-(4-fluoro-benzo-yl)hydra-zine-1-carbono-thio-yl]benzamide.

In the title compound, C15H11F2N3O2S, the dihedral angle between the fluoro-benzene rings is 88.43 (10)° and that between the central semithiocarbazide grouping is 47.00 (11)°. The dihedral angle between the amide group and attached fluoro-benzene ring is 50.52 (11)°; the equivalent angle between the carbonyl-thio-amide group and its attached ring is 12.98 (10)°. The major twists in the mol-ecule occur about the C-N-N-C bonds [torsion angle = -138.7 (2)°] and the Car-Car-C-N (ar = aromatic) bonds [-132.0 (2)°]. An intra-molecular N-H⋯O hydrogen bond occurs, which generates an S(6) ring. In the crystal, the mol-ecules are linked by N-H⋯O and N-H⋯S hydrogen bonds, generating (001) sheets. Weak C-H⋯O and C-H⋯F inter-actions are also observed.

(E)-3-Chloro-N'-(2-fluoro-benzyl-idene)thio-phene-2-carbohydrazide.

The title compound, C12H8ClFN2OS, is a hydrazide derivative adopting an E conformation with an azomethine N=C double bond length of 1.272 (2) Å. The mol-ecular skeleton is approximately planar; the terminal five- and six-membered rings form a dihedral angle of 5.47 (9)°. In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen bonds into zigzag chains propagating in [100].

N-[Eth-yl(2-hy-droxy-eth-yl)carbamo-thio-yl]-3-fluoro-benzamide.

In the title compound, C12H15FN2O2S, the mol-ecule adopts a cis configuration of the fluoro-benzoyl group with respect to the thiono group about their C-N bond. The dihedral angle between the fluoro-benzoyl group and the thio-urea N2CS fragment is 69.60 (11)°. An intra-molecular N-H⋯O hydrogen bond occurs. In the crystal, mol-ecules form chains along the b-axis direction via O-H⋯S and C-H⋯O hydrogen bonds.

N-[Eth-yl(2-hy-droxy-eth-yl)carbamo-thio-yl]-2-methyl-benzamide.

The title compound, C13H18N2O2S, adopts a cis conformation between the methyl-benzoyl and thiono groups across their thio-urea C-N bond. However, the methyl-benzoyl group and N2CS thio-urea moiety are twisted by 15.03 (3)°. In the molecule there is an N-H⋯O hydrogen bond. In the crystal, mol-ecules are linked by O-H⋯O inter-actions, generating chains extending along the c-axis direction.

Synthesis, characterization, X-ray structure and biological activities of C-5-bromo-2-hydroxyphenylcalix[4]-2-methyl resorcinarene.

C-5-bromo-2-hydroxyphenylcalix[4]-2-methylresorcinarene (I) was synthesized by cyclocondensation of 5-bromo-2-hydroxybenzaldehyde and 2-methylresorcinol in the presence of concentrated HCl. Compound I was characterized by infrared and nuclear magnetic resonance spectroscopic data. X-ray analysis showed that this compound crystallized in a triclinic system with space group of Pi, a = 15.9592(16)Å, b = 16.9417(17)Å, c = 17.0974(17)Å, α = 68.656(3)°, ß = 85.689(3)°, γ = 81.631(3)°, Z = 2 and V = 4258.6(7)Å3. The molecule adopts a chair (C2h) conformation. The thermal properties and antioxidant activity were also investigated. It was strongly antiviral against HSV-1 and weakly antibacterial against Gram-positive bacteria. Cytotoxicity testing on Vero cells showed that it is non-toxic, with a CC50 of more than 0.4 mg/mL.

3-Chloro-N-[N-(furan-2-carbon-yl)hydrazinocarbo-thio-yl]benzamide.

In the title compound C13H10ClN3O3S, the benzoyl group maintains its trans conformation against the thiono group about the C-N bond and the intra-molecular hydrogen bond between the benzoyl O atom and thio-amide H atom. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules, forming chains along the b-axis direction. In addition, C-H⋯π inter-actions occur between a phenyl H atom and the furan ring.

1-(2-Chloro-phen-yl)-3-(2-ethyl-hexa-noyl)thio-urea.

In the title compound, C15H21ClN2OS, the central chromophore moiety (C2N2OS) is approximately planar, with a maximum deviation of -0.027 (1) Å, and is oriented at a dihedral angle of 86.7 (1)° with respect to the chloro-phenyl ring. An intra-molecular N-H⋯O hydrogen bond stabilizes the mol-ecular conformation. In the crystal, mol-ecules associate via N-H⋯S hydrogen bonds, forming inversion dimers with motif R 2 (2)(8). These dimers are further connected by N-H⋯O hydrogen bonds, forming R 2 (2)(12) dimers. As a result, hydrogen-bonded chains running along [110] are formed. C-H⋯S inter-actions also occur. The terminal two C atoms of the butyl chain are disordered over two positions with an occupancy ratio of 0.54:0.46.

1-(4-Chlorophenyl)-3-(3-chloro-pro-pionyl)thio-urea.

In the title compound, C10H10Cl2N2OS, the mol-ecule adopts a trans-cis conformation with respect to the position of the carbonyl group and the chloro-phenyl groups relative to the thiono group across the C-N bonds. The mol-ecule is stabilized by an N-H⋯O hydrogen bond. In the crystal, mol-ecules are linked by N-H⋯S and C-H⋯O hydrogen bonds, forming zigzag chains along the b-axis direction. C-H⋯π inter-actions are also present.