RESUMEN

Four new triorganotin(IV) complexes with general formula R3SnL (R=C4H9, C6H5, and L=3-[(fluorophenylamido)]propenoic acid, 3-[(fluorophenylamido)]propanoic acid) were synthesized and characterized by elemental analyses, FT-IR, NMR ((1)H, (13)C and (119)Sn), mass spectrometry and single crystal X-ray structural analysis. The disappearance of the OH peak of the carboxylic acid in the FT-IR and NMR spectra of the compounds conform the formation of the compound and suggests that the complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date shows the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than 250. Crystallographic data for compound 2 showed that tin has distorted tetrahedral geometry with 433.42° angle around the central tin atom. The compounds (1-4) bind to DNA, resulting hypochromism shifts in UV-visible spectroscopy suggesting an intercalative mode of interactions. The compound-DNA interaction results (UV-visible and Viscometery) encourage using the compounds against HCV. The compounds (1-4) were screened for anti-HCV activity using Huh7.5 cell (human hepatoma cell) by the Gaussia Luciferase Assay and found to be biologically active. Based on Gaussia Luciferase Assay, compound 3 (Tributylstannic [3-(2-fluorophenylamido)propionate]) was taken for quantitative analysis by "QRT-PCR" using the serum of HCV patients and was found to have substantial anti-HCV activity. This work, demonstrated that compound 3 may be used as a potential anti-HCV agent in the future.

Asunto(s)

Complejos de Coordinación/síntesis química , Compuestos Orgánicos de Estaño/química , Ácidos Carboxílicos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/química , Cristalografía por Rayos X , ADN/química , ADN/metabolismo , Flúor/química , Humanos , Ligandos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Espectroscopía Infrarroja por Transformada de Fourier , Viscosidad

RESUMEN

Three new organotin(iv) carboxylates () of 3,5-dimethylbenzoate, have been synthesized and characterized by elemental analysis, FT-IR, multinuclear NMR ((1)H, (13)C and (119)Sn), mass spectrometry and single crystal X-ray structural analysis. Crystallographic data show that in compounds and , the geometry at the central Sn atom is skew-trapezoidal bipyramidal while compound displays a distorted trigonal bipyramidal coordination geometry. In the case of compounds and , the asymmetric chelating mode of the carboxylate groups is reflected in the unequal C-O bond distances, those observed for the O1 and O3 oxygen atoms being significantly longer than those found in the O2 and O4 atoms. In the case of compound , the carboxylate groups bridge asymmetrically adjacent tin atoms in an anti-syn mode generating polymeric zigzag chains running parallel to the crystallographic c-axis. The compounds were screened for anti-HCV (hepatitis C virus) potency by the Gaussia luciferase assay using infected Huh 7.5 cells (human hepatocellular cell). Structure-activity relationship studies led to the identification of dibutyltin(iv)bis(3,5-dimethylbenzoic acid) (compound ) as a potent HCV inhibitor, with log IC50 values equal to 0.69 nM in the cell-based assay. Compound was further subjected to quantitative analysis using real-time PCR assays and viral RNA count vs. drug concentration confirmed the Gaussia luciferase assay results. The HCV RNA targeting mode of the compounds () was confirmed by a compound-DNA interaction study. The compounds ()-DNA interactions were investigated by UV-vis spectroscopy and viscometry. The hypochromic effect in spectroscopy evidenced an intercalative mode of interaction with the binding affinity in the order of > > .

Asunto(s)

Antivirales , Benzoatos , Complejos de Coordinación , Compuestos Orgánicos de Estaño , Antivirales/síntesis química , Antivirales/química , Antivirales/farmacología , Benzoatos/química , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Cristalografía por Rayos X , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Humanos , Resonancia Magnética Nuclear Biomolecular , Compuestos Orgánicos de Estaño/síntesis química , Compuestos Orgánicos de Estaño/química , Compuestos Orgánicos de Estaño/farmacología , ARN Viral/análisis , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

In the title compound, C(10)H(9)NO(4), the 2-hy-droxy-anilinic and the 4-oxobut-2-enoic acid groups are almost planar, with r.m.s. deviations of 0.0086 and 0.0262 Å, respectively. The dihedral angle between the two groups is 6.65 (1)°. Intra-molecular N-H⋯O, C-H⋯O and O-H⋯O hydrogen bonds form S(5), S(6) and S(7) ring motifs. In the crystal, the mol-ecules are dimerized due to C-H⋯O and O-H⋯O inter-molecular hydrogen bonds, with R(2) (2)(8) ring motifs. The dimers are inter-linked into polymeric chains along [010] with R(4) (3)(13) ring motifs by C-H⋯O, N-H⋯O and O-H⋯O hydrogen bonds.

RESUMEN

In the title compound, C(10)H(9)Cl(2)NO(3), inversion dimers occur due to pairs of inter-molecular O-H⋯O hydrogen bonds from the carboxyl groups forming R(2) (2)(8) loops. The dimers are linked into C(4) chains along the a axis by inter-molecular N-H⋯O links. A short intra-molecular C-H⋯O contact occurs in the mol-ecule.

RESUMEN

The crystal structure of the title compound, C(10)H(10)FNO(3), contains dimers of the asymmetric unit, with R(2) (2)(8) rings arising from inter-molecular O-H⋯O hydrogen bonding through the carboxyl-ate groups. Adjacent dimeric units are connected to each other through one N-H⋯O and two C-H⋯O inter-molecular hydrogen bonds. C-H⋯O hydrogen bonds involving the aromatic ring and the O atoms of two carboxyl-ate groups form an R(3) (3)(7) ring. The crystal structure is further stabilized by C-H⋯F inter-actions, giving rise to a three-dimensional network.

RESUMEN

The crystal structure of the title compound, C(10)H(9)Cl(2)NO(3), consists of dimers due to inter-molecular O-H⋯O hydrogen bonding forming an R(2) (2)(8) ring through the carboxyl- groups. These dimers are linked to each other by inter-molecular hydrogen bonds between the amine group and the adjacent carbonyl O atom. A single C-Cl⋯π inter-action is also observed between the chloro-substituted aromatic rings.