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Crystal structure, DNA binding studies, nucleolytic property and topoisomerase I inhibition of zinc complex with 1,10-phenanthroline and 3-methyl-picolinic acid

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Abstract

Crystal structure analysis of the zinc complex establishes it as a distorted octahedral complex, bis(3-methylpicolinato-κ2 N,O)2(1,10-phenanthroline-κ2 N,N)-zinc(II) pentahydrate, [Zn(3-Me-pic)2(phen)]·5H2O. The trans-configuration of carbonyl oxygen atoms of the carboxylate moieties and orientation of the two planar picolinate ligands above and before the phen ligand plane seems to confer DNA sequence recognition to the complex. It cannot cleave DNA under hydrolytic condition but can slightly be activated by hydrogen peroxide or sodium ascorbate. Circular Dichroism and Fluorescence spectroscopic analysis of its interaction with various duplex polynucleotides reveals its binding mode as mainly intercalation. It shows distinct DNA sequence binding selectivity and the order of decreasing selectivity is ATAT > AATT > CGCG. Docking studies lead to the same conclusion on this sequence selectivity. It binds strongly with G-quadruplex with human tolemeric sequence 5′-AG3(T2AG3)3-3′, can inhibit topoisomerase I efficiently and is cytotoxic against MCF-7 cell line.

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Acknowledgments

The authors like to thank MOSTI of Malaysia for an Science grant (02-02-11-SF0033). IC thanks CNPq (Proc. 472237/2008-0) and Fundunesp (Proc. 00525/08-DFP).

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Authors and Affiliations

  1. Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, 53300, Kuala Lumpur, Malaysia

    Hoi-Ling Seng, Sze-Tin Von & Chew-Hee Ng

  2. Chemistry Department, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Kong-Wai Tan, Mohd Jamil Maah & Seik-Weng Ng

  3. Faculty of Biotechnology and Molecular Biology, Universiti Putra Malaysia, 43400, Serdang, Malaysia

    Raja Noor Zaliha Raja Abd Rahman

  4. BioMat—Departamento de Física, Faculdade de Ciências, São Paulo State University, UNESP, Bauru, 17015-970, Brazil

    Ignez Caracelli

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  1. Hoi-Ling Seng
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Seng, HL., Von, ST., Tan, KW. et al. Crystal structure, DNA binding studies, nucleolytic property and topoisomerase I inhibition of zinc complex with 1,10-phenanthroline and 3-methyl-picolinic acid. Biometals 23, 99–118 (2010). https://doi.org/10.1007/s10534-009-9271-y

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