Synthesis of Oxovanadium(IV) Schiff base Complexes derived from C-substituted Diamines and Pyridoxal-5-Phosphate as Antitumor Agents

被引:35
作者
Hazari, Puja Panwar [1 ]
Pandey, Anand Kumar [1 ,2 ]
Chaturvedi, Shubhra [1 ]
Tiwari, Anjani Kumar [1 ]
Chandna, Sudhir [3 ]
Dwarakanath, Bilikere Srinivasarao [3 ]
Mishra, Anil Kumar [1 ]
机构
[1] Inst Nucl Med & Allied Sci, Div Cyclotron & Radiopharmaceut Sci, New Delhi 110054, India
[2] Banaras Hindu Univ, Inst Technol, Sch Biomed Engn, Varanasi 221005, Uttar Pradesh, India
[3] Inst Nucl Med & Allied Sci, Div Radiat Biosci, New Delhi 110054, India
关键词
bifunctional chelating agent; chemical nucleases; cytotoxicity; DNA modification; pyridoxal-5-phosphate; Schiff base; vanadium complex; HYDROGEN-PEROXIDE; LIPID-PEROXIDATION; DNA CLEAVAGE; VANADIUM; SALICYLALDEHYDE; CHEMISTRY; MECHANISM; CANCER;
D O I
10.1111/j.1747-0285.2011.01265.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 VOSO4. 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.
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页码:223 / 234
页数:12
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