title: Organotin(IV) based anti-HCV drugs: synthesis, characterization and biochemical activity.
abstract: 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 > > .
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Farooq Ali
authors.initials: FA
authors.lastname: Shah
authors.forename: Shaista
authors.initials: S
authors.lastname: Sabir
authors.forename: Kaneez
authors.initials: K
authors.lastname: Fatima
authors.forename: Saqib
authors.initials: S
authors.lastname: Ali
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Qadri
authors.forename: Corrado
authors.initials: C
authors.lastname: Rizzoli
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001565:Benzoates / Q000737:chemistry; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009947:Organotin Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012367:RNA, Viral / Q000032:analysis; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000998:Antiviral Agents; D001565:Benzoates; D056831:Coordination Complexes; D009947:Organotin Compounds; D012367:RNA, Viral; C094650:3,5-dimethylbenzoic acid