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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| Authors: | Hoi-Ling Seng Sze-Tin Von Kong-Wai Tan Mohd Jamil Maah Seik-Weng Ng Raja Noor Zaliha Raja Abd Rahman Ignez Caracelli Chew-Hee Ng |
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| Institution: | 1.Faculty of Engineering and Science,Universiti Tunku Abdul Rahman,Kuala Lumpur,Malaysia;2.Chemistry Department,University of Malaya,Kuala Lumpur,Malaysia;3.Faculty of Biotechnology and Molecular Biology,Universiti Putra Malaysia,Serdang,Malaysia;4.BioMat—Departamento de Física, Faculdade de Ciências,S?o Paulo State University, UNESP,Bauru,Brazil |
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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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