Discovery of novel multi-substituted benzo-indole pyrazole schiff base derivatives with antibacterial activity targeting DNA gyrase.

The design and synthesis of novel multi-substituted benzo-indole pyrazole Schiff base derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activities against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella. In addition, we selected 20 compounds for the in vitro antibacterial activities assay of 6 drug-resistant bacteria strains. The result revealed compound 8I-w exhibited excellent antibacterial activity against 4 drug-resistant E. coli bacteria strains with IC50 values of 7.0, 17.0, 13.5, and 1.0 µM, respectively. In vitro enzyme inhibitory assay showed that compound 8I-w displayed potent inhibition against DNA gyrase with IC50 values of 0.10 µM. The molecular docking model indicated that compounds 8I-w can bind well to the DNA gyrase by interacting with various amino acid residues. This study demonstrated that the compound 8I-w can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.

Novel coumarin-thiazolyl ester derivatives as potential DNA gyrase Inhibitors: Design, synthesis, and antibacterial activity.

The design and synthesis of novel coumarin-thiazolyl ester derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activity against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8p exhibited excellent antibacterial activity against four bacteria strains with MIC values of 0.05, 0.05, 8, and 0.05 µg/mL, respectively. In vitro drug-resistant bacterial inhibition experiments indicated that compound 8p exhibited the best bacteriostatic effect in the selected compounds and four positive control drugs with MIC values of 4 µg/mL. In vitro enzyme inhibitory assay showed that compound 8p exhibited potent inhibition against DNA gyrase with IC50 values of 0.13 µM. The molecular docking model indicated that compounds 8p can bind well to the DNA gyrase by interacting with amino acid residues. This study demonstrated that the compound 8p can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.

A bioactivity-oriented modification strategy for SDH inhibitors with superior activity against fungal strains.

In this work, a total of 36 novel 5-(nicotinamido)-1-phenyl-1H-pyrazole-4-carboxylic acid derivatives were designed and synthesized successfully by introducing a carboxyl group based on the N-(1-(4-chlorophenyl)-4-cyano-1H-pyrazol-5-yl)-6-methoxynicotinamide. Among them, the growth inhibition assays on agar plates showed that compound 5IV-d(5-(2-chloronicotinamido)-1-(p-tolyl)-1H-pyrazole-4-carboxylic acid) exhibited the significant antifungal activity against four important fruit and main crop disease fungi (i.e., Valsa mali Miyabe et Yamada, Botryosphaeria dothidea, Helminthosporium maydis and Rhizoctonia cerealis) with EC50 values of 22.6, 14.5, 17.6 and 18.2 µM, respectively. In addition, 5IV-d showed the excellent inhibitory effect against SDH enzymes with IC50 values ranging from 9.4 to 15.6 µM. In vivo bioassay and molecular docking were applied to explore the potential in practical application and combination of modified structure and SDH. The results of structure-activity relationships indicates that the methoxy substitution at the benzene ring attached to the pyrazole ring and a wide variety of substituents could be responsible for the promising antifungal efficacy of the designed compounds. This study demonstrated that the compound 5IV-d can act as the most potent SDH inhibitor in the reported series of compounds.

Poly[[hexa-aqua-(µ(3)-2,2'-bipyridine-4,4',6,6'-tetra-carboxyl-ato-κ(6)O(4):N,O(6),O(6'),N':O(4'))dinickel(II)] dihydrate].

In the title complex, {[Ni(2)(C(14)H(4)N(2)O(8))(H(2)O)(6)]·2H(2)O}(n), the two Ni(II) atoms are located in different special positions (one on a twofold rotation axis and the second on a centre of symmetry) and have different distorted octa-hedral environments (one by two N atoms from a bipyridine unit, two O atoms from two water mol-ecules and two O atoms from two carboxyl-ate groups, and the second by four O atoms from four water mol-ecules and two O atoms from two carboxyl-ate groups). Thus, the environments of the Ni(II) atoms may be denoted as NiN(2)O(4) and NiO(6). In the crystal, there exists an extensive network of classical O-H⋯O hydrogen bonds.

1,3-Bis(3,5-dimethyl-phen-yl)-5-methyl-benzene.

In the title compound, C(23)H(24), the dihedral angles formed by the central benzene ring with the peripheral benzene rings are 29.90 (5) and 34.95 (5)°. The crystal packing is stabilized by π-π stacking inter-actions with centroid-centroid distances of 3.815 (4) Å.

1-Methyl-3,5-bis-(3-methyl-phen-yl)benzene.

In the title compound, C(21)H(20), the dihedral angles formed by the central benzene ring with the outer benzene rings are 21.43 (6) and 31.70 (4)°. The crystal packing is stabilized by a weak π-π stacking inter-action, with a centroid-centroid distance of 3.843 (3) Å.

Bis[µ-3-(1H-benzimidazol-2-yl)benzoato]dicopper(I).

The dimeric title complex, [Cu(2)(C(14)H(9)N(2)O(2))(2)], resides on a center of symmetry. In the crystal, the mol-ecules are packed via π-π stacking inter-actions alternating between imidazole and benzene rings [mean inter-planar distances = 3.754 (3) and 3.624 (3) Å]. An inter-molecular N-H⋯O hydrogen bond links the dimers together. The two-coordinate Cu(I) atom displays an O-Cu-N bond angle of 176.3 (2)°. The Cu⋯Cu distance within the dimer is 5.100 (2) Å.

Bis{2-[(E)-benzyl-imino-meth-yl]-4-methyl-phenolato-κN,O}nickel(II).

In the title complex, [Ni(C(15)H(14)NO)(2)], the Ni(II) atom is located on an inversion centre and is coordinated by two O and two N atoms from two symmetry-related bidentate Schiff base ligands in a slightly distorted square-planar geometry. The phenyl and benzene rings in the ligand mol-ecule form a dihedral angle of 72.79 (8)°.

2,4-Dibromo-6-{(E)-[(R)-1-phenyl-ethyl]imino-meth-yl}phenol.

In the title Schiff base, C(15)H(13)Br(2)NO, the benzene and phenyl rings form a dihedral angle of 75.18 (13)°. The N=C bond length of 1.263 (6) Šis shorter than of the N-C bond [1.476 (5) Å], indicating a double bond. In the crystal, there is some pseudosymmetry. This occurs because most of the two mol-ecules are centrosymmetrically related. The mol-ecular structure is stabilized by intra-molecular O-H⋯N hydrogen bonds.