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Synthesis and characterization of new transition metal {Cu(II), Ni(II) and Co(II)} l-phenylalanine–DACH conjugate complexes: In vitro DNA binding, cleavage and molecular docking studies

Paper ID Volume ID Publish Year Pages File Format Full-Text
29754 44436 2014 11 PDF Available
Title
Synthesis and characterization of new transition metal {Cu(II), Ni(II) and Co(II)} l-phenylalanine–DACH conjugate complexes: In vitro DNA binding, cleavage and molecular docking studies
Abstract

•Synthesis of l-phenylalanine–DACH conjugate Cu(II)/Ni(II)/Co(II) complexes.•Preliminary in vitro binding profile of the complexes with CT-DNA.•Complex 1 displayed an impressive pBR322 DNA nuclease activity.•1 Exhibited significant inhibitory effects on Topo-I catalytic activity.•Validation by molecular docking studies.

The novel metal-based molecular entities {Cu(II), Ni(II) and Co(II)} 1–3, respectively were synthesized and characterized by elemental analysis and spectroscopic methods (IR, 1H and 13C NMR, EPR, UV–vis, ESI–MS and XRPD). The interaction studies of 1–3 with CT DNA have been investigated by UV–vis titrations, fluorescence and circular dichroic studies which revealed the electrostatic mode of binding and on the basis of intrinsic binding constant Kb (5.30 × 104, 1; 3.41 × 104, 2; and 2.74 × 104, 3; M−1), the extent of DNA binding was ascertained, following the order 1 > 2 > 3. Specifically, 1 exhibited greater binding propensity with CT DNA, therefore the cleavage activity of 1 with pBR322 DNA was evaluated by agarose gel electrophoresis assay. Complex 1 presented an impressive nuclease activity generating single- and double-strand breaks. Further mechanistic investigation revealed the efficiency of 1 to cleave DNA strands by an oxidative pathway involving the generation of ROS and preferential selectivity towards the DNA minor groove. Moreover, complex 1 exhibited significant inhibitory effects on the catalytic activity of topoisomerase I at a very low concentration ∼20 μM. Additionally, computer-aided molecular docking techniques were carried out to correlate and rationalize the observed binding affinities with docking studies towards the molecular target DNA and Topo-I.

Graphical abstractDNA binding and Topo-I inhibition by copper(II) complex of l-phenylalanine–DACH conjugate, 1.Figure optionsDownload full-size imageDownload as PowerPoint slide

Keywords
Cu(II)–DACH conjugate complex; CT DNA binding studies; Thermal denaturation; pBR322 plasmid cleavage; Topo-I inhibition
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Synthesis and characterization of new transition metal {Cu(II), Ni(II) and Co(II)} l-phenylalanine–DACH conjugate complexes: In vitro DNA binding, cleavage and molecular docking studies
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 136, 5 July 2014, Pages 1–11
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us