Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Road, New Delhi 110054, India.
Chem Biol Drug Des. 2012 Feb;79(2):223-34. doi: 10.1111/j.1747-0285.2011.01265.x. Epub 2012 Jan 4.
Oxovanadium (IV) complexes of N,N'-bispyridoxyl-5, 5'-bis (phosphate) ethylenediimine (L1) and N,N'-bis(pyridoxyl)-5,5'-bis(phosphate)-1''-(p-nitrobenzyl)ethylenediimine (L2) were synthesized by condensation of optically active C-substituted diamines and pyridoxal-5-phosphate. Oxovanadium (IV) complexes derived from L1 and L2 were evaluated as DNA cleavage agent (cleavage of supercoiled plasmid pBR322 DNA). Interestingly, both the oxovanadium (IV) complexes exhibited DNA nuclease activity, and the extent of oxidation of DNA by these vanadyl complexes was superior to VOSO(4) . The significant reduction in primary tumor and increased delay in tumor growth of 15 days was seen in the tumor regression analysis with oxovanadium (IV) complex of L1. With the preliminary studies performed with the pyridoxal-5-phosphate -based salen derivatives including the cytotoxicity and tumor regression, it is evident that the salen bifunctional chelating agent has obtained therapeutic potential if conjugated to a gene-specific targeting molecule for the oxidation of guanine residue.
氧钒(IV)配合物的 N,N'-双吡啶-5,5'-双(磷酸)乙二胺（L1）和 N,N'-双（吡啶醛）-5,5'-双(磷酸)-1''-(对硝基苄基)乙二胺（L2）通过手性 C-取代二胺和吡哆醛-5-磷酸缩合合成。从 L1 和 L2 衍生的氧钒(IV)配合物被评估为 DNA 切割剂（超螺旋质粒 pBR322 DNA 的切割）。有趣的是，两种氧钒(IV)配合物都表现出 DNA 核酸酶活性，并且这些钒氧配合物对 DNA 的氧化程度优于 VOSO(4)。在用 L1 的氧钒(IV)配合物进行肿瘤回归分析时，观察到原发性肿瘤的显著减少和肿瘤生长的 15 天延迟增加。初步研究表明，基于吡哆醛-5-磷酸的席夫碱衍生物具有细胞毒性和肿瘤回归作用，如果与基因特异性靶向分子结合用于鸟嘌呤残基的氧化，那么它具有获得治疗潜力。
