New modulated design and synthesis of chiral Cu^II/Sn^IV bimetallic potential anticancer drug entity: In vitro DNA binding and pBR322 DNA cleavage activity

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• 作者：Sartaj Tabassum ; ^{tsartaj62@yahoo.com} ; Girish Chandra Sharma ; Farukh Arjmand
• 关键词：5&prime ; -GMP ; Nuclease activity ; Groove binding ; Hydrolytic cleavage ; CT DNA ; pBR322 DNA
• 刊名：Spectrochimica Acta Part A ; Molecular and Biomolecular Spectroscopy
• 出版年：2012
• 期刊代码：99_13861425
• 类别：ch
• 出版时间：May, 2012
• 卷：90
• 期：Complete
• 页码：208-217
• 文件大小：1067 K

摘要

A new chiral ligand scaffold dFont">L derived from (R)-2-amino-2-phenyl ethanol and diethyl oxalate was isolated and thoroughly characterized by various spectroscopic methods. The ligand dFont">L was allowed to react with CuCl₂路2H₂O and NiCl₂路6H₂O to achieve monometallic complexes dFont">1 and dFont">2, respectively. Subsequently modulation of dFont">1 and dFont">2 was carried out in the presence of SnCl₄路5H₂O to obtain heterobimetallic potential drug candidates dFont">3 and dFont">4 possessing (Cu^II/Sn^IV and Ni^II/Sn^IV) metallic cores, respectively and characterized by elemental analysis and spectroscopic data including ¹H, ¹³C and ¹¹⁹Sn NMR in case of dFont">3 and dFont">4. In vitro DNA binding studies revealed that complex dFont">3 avidly binds to DNA as quantified by K_b and K_sv values. Complex dFont">3 exhibits a remarkable DNA cleavage activity (concentration dependent) with pBR322 DNA and the cleavage activity of dFont">3 was significantly enhanced in the presence of activators and follows the order H₂O₂ > Asc > MPA > GSH. Complex dFont">3 cleave pBR322 DNA via hydrolytic pathway and accessible to major groove of DNA.