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DNA-Binding Studies and Antitumor Evaluation of Novel Water Soluble Organic pip and hpip Analogs

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Abstract

Two new water-soluble pip and hpip analogs, 1 and 2 pip = 2-phenylimidazo[4,5-f][1, 10]phenanthroline; hpip = 2-(2-hydroxyphenyl)imidazo[4,5-f][1, 10]phenanthroline, have been synthesized and fully characterized by CHN analysis, MALDI-TOF MS, 1H-NMR, IR (ATR), and UV–Vis methods. The DNA-binding behaviors of both compounds have been studied by viscosity measurements, spectroscopic methods, and gel electrophoresis studies, and potential for antitumor activity was evaluated by measuring their ability to inhibit DNA transcription. The results indicate that both compounds show some strong binding to DNA in a mixture of electrostatic and intercalative mode resulting in the intrinsic binding constants Kb of (4.0 ± 0.5) × 105 M−1 and (7.5 ± 0.5) × 105 M−1 for 1 and 2, respectively. These strong binding affinities for DNA are comparable for that seen for many transition metal-based intercalators. Comparatively, observed difference in the DNA-binding affinities of two complexes can be reasonably explained by the presence of an intra-molecular hydrogen-bonding between the ortho-phenolic group and the nitrogen atom of the imidazole ring. The extended co-planarity of 2 due to the intramolecular hydrogen bonding may lead to an enhancement of DNA binding affinity of 2. In addition, 2 can promote cleavage of pBR322 DNA upon irradiation, it inhibits DNA transcription and it is more cytotoxic at lower concentrations in comparison to 1, as revealed by the spectroscopic measurements.

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Acknowledgments

The authors are grateful to the supports of Bulent Ecevit University for grant 2011-03-13-06. The authors also thank to Assoc. Prof. Stephen Ralph at the Wollongong University for his support and Dr. Zehra Safi Oz for the use of her laboratory to make it possible to visualize and photograph the gel electrophoresis results.

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  1. Department of Chemistry, Faculty of Arts and Sciences, Bulent Ecevit University, Zonguldak, 67100, Turkey

    Burak Coban & Ufuk Yildiz

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Correspondence to Burak Coban.

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Coban, B., Yildiz, U. DNA-Binding Studies and Antitumor Evaluation of Novel Water Soluble Organic pip and hpip Analogs. Appl Biochem Biotechnol 172, 248–262 (2014). https://doi.org/10.1007/s12010-013-0513-7

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