کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1392987 | 1501167 | 2012 | 10 صفحه PDF | دانلود رایگان |
A novel heterobimetallic CuII–SnIV complex 1 bearing bioactive 1,10-phenanthroline pharmacophore ligand scaffold was synthesized and characterized by elemental analysis, IR, UV–vis spectroscopy, Mass (ESI and FAB) and X–ray crystallography. The in vitro DNA binding studies of complex 1 with CT DNA was carried out by various biophysical and molecular docking techniques which revealed that complex 1 binds to DNA through intercalation in the minor groove having AT-rich sequences. Complex 1 exhibits high chemical nuclease activity cleaving supercoiled pBR322 DNA via hydrolytic pathway which was further evidenced by T4 DNA ligase assay. The complex 1 shows high inhibitory activity against Topo I at a very low concentration (15 μM), suggesting that complex 1 is an efficient catalytic inhibitor of human Topo I and further validated by molecular docking studies.
To elucidate the molecular recognition toward the minor groove of DNA as Topo I inhibitor, molecular docking techniques were performed and further validated by various spectroscopic studies.Figure optionsDownload as PowerPoint slideHighlights
► Novel heterobimetallic CuII–SnIV complex 1 bearing bioactive 1,10-phenanthroline pharmacophore ligand scaffold.
► The in vitro DNA binding studies reveal that this complex bind to CT DNA via intercalation into the minor groove.
► Complex 1 shows efficient hydrolytic cleavage of pBR322 DNA as evidenced from the T4 DNA ligase experiments.
► The complex showed an IC50 of 15 μM, indicates that it has high potential to act as an anticancer drug.
Journal: European Journal of Medicinal Chemistry - Volume 49, March 2012, Pages 141–150