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 > > .

Synthesis, Characterization, Biological Activity and Molecular Docking Studies of Novel Organotin(IV) Carboxylates

“…Organotin(IV) carboxylates are found be the most promising alternatives, as these have shown higher apoptosis inducing character compared to the platinum complexes, both in vivo and in vitro ( Indumathy et al, 2007 ; Butt et al, 2019 ). In addition to the anticancer potential, organotin(IV) carboxylates also possess significant antibacterial, antifungal, insecticidal, anti-tuberculosis and antidiabetic activities ( Kovala-Demertzi et al, 2009 ; Tzimopoulos et al, 2010 ; Tariq et al, 2013 ; Sirajuddin et al, 2014a ; Sirajuddin et al, 2014b ; Shah et al, 2015 ; Tariq et al, 2016 ; Debnath et al, 2019 ; Sirajuddin et al, 2021 ).…”

New triorganotin(IV) complexes of quinolone antibacterial drug sparfloxacin: Synthesis, structural characterization, DFT studies and biological activity

“…The chemistry of organotin(IV) compounds has grown enormously in the past few decades as one of the strongest areas in the interdisciplinary organometallic field owing to their structural diversity and broad range of industrial, agricultural and biological applications . Their peculiar structural diversity arises due to the fact that tetravalent Sn atoms usually expand their coordination numbers and become hypervalent on inter‐ and/or intramolecular interactions with electron donor atoms owing to the large size of Sn atom, the availability of low‐lying empty 5d atomic orbitals, and pronounced electron‐acceptor ability of the Sn atoms .…”

Preparation, structural elucidation and biocidal applications of trimethyltin(IV) complexes derived from substituted carboxylic acids

“…In continuation to our preceding work [ 19 , 20 , 21 , 22 , 23 ], we report herein the synthetic route, characterization and a few important biocidal activities of these organotin derivatives (1-7) to further unravel their structural and biological aspects. Keeping in view the medicinal importance of carboxylic acids, they are complexed with the triorganotin(IV) moiety for exploring their biological significance [ 24 , 25 ]. The results obtained here are quite promising ones and the facts showed that they could furnish a key scaffold for enhanced antimicrobial activity, but structural alterations/modifications should be the prerequisites in determining their therapeutic potential for future drug discovery processes.…”