Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 87, Issue -, Pages 168-174Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.09.057
Keywords
Pyrrole-polyamide dimer; EDTA analogue; Ce(IV) complex; Hydrolytic DNA cleavage; Cytotoxicity
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Funding
- National Natural Science Foundation of China [21402085]
- Program for New Century Excellent Talents in University [NCET-11-0920]
- Guangdong Provincial Department of Science and Technology of China [2012B050100007]
- Department of Education of Guangdong Province [2012KJCX0024]
- Southern Medical University
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Two EDTA analogue-tethered C-2-symmetrical dimeric monopyrrole-polyamide 5 and dipyrrole-polyamide 6, and their corresponding Ce(IV) complexes Ce-5 and Ce-6 were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicate that complexes Ce-5 and Ce-6 exhibited potent DNA-cleaving activities under physiological conditions. The maximal first-order rate constants (k(max)'s) were (0.42 +/- 0.02) h(-1) for Ce-5 and (0.52 +/- 0.02) h(-1) for Ce-6, respectively, suggesting that both complexes catalyzed the cleavage of supercoiled DNA by up to approximately 10(8)-fold. Complex Ce-6 exhibited ca 10-fold higher overall catalytic activity (k(max)/K-M) than Ce-5, which may be ascribed to its higher DNA-binding affinity. Inhibition experiments and a model study convincingly suggest that both complexes Ce-5 and Ce-6 functioned as hydrolytic DNA-cleavers. In addition, both complexes were found to display moderate inhibitory activity toward A549 and HepG-2 cells. (C) 2014 Elsevier Masson SAS. All rights reserved.
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