DNA-Binding and Cytotoxicity of Copper(I) Complexes Containing Functionalized Dipyridylphenazine Ligands.

Sammar Alsaedi,Bandar A Babgi,Mariusz Jaremko,Muhammad N Arshad,Magda H Abdellattif,Mostafa A Hussien,Abdullah M Asiri,Abdul-Hamid M Emwas,Mark G Humphrey

doi:10.3390/pharmaceutics13050764

Abstract

A set of copper(I) coordination compounds with general formula [CuBr(PPh3)(dppz-R)] (dppz-R = dipyrido[3,2-a:2’,3’-c]phenazine (Cu-1), 11-nitrodipyrido[3,2-a:2’,3’-c]phenazine (Cu-2), 11-cyanodipyrido[3,2-a:2’,3’-c]phenazine (Cu-3), dipyrido[3,2-a:2’,3’-c]phenazine-11-phenone (Cu-4), 11,12-dimethyldipyrido[3,2-a:2’,3’-c]phenazine (Cu-5)) have been prepared and characterized by elemental analysis, 1H-NMR and 31P-NMR spectroscopies as well as mass spectrometry. The structure of Cu-1 was confirmed by X-ray crystallography. The effect of incorporating different functional groups on the dppz ligand on the binding into CT-DNA was evaluated by absorption spectroscopy, fluorescence quenching of EtBr-DNA adducts, and viscosity measurements. The functional groups affected the binding modes and hence the strength of binding affinities, as suggested by the changes in the relative viscosity. The differences in the quenching constants (Ksv) obtained from the fluorescence quenching assay highlight the importance of the functional groups in altering the binding sites on the DNA. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA changing with the different functional groups. Evaluation of the anticancer activities of the five copper compounds against two different cancer cell lines (M-14 and MCF-7) indicated the importance of the functional groups on the dppz ligand on the anticancer activities. Among the five copper complexes, the cyano-containing complex (Cu-3) has the best anticancer activities.

Highlights

The field of metallodrugs has been under scrutiny since the discovery of the anticancer properties of cis-diamminedichloroplatinum(II)
We extend our studies to examine the effect of functionalizing the ies to examine the effect of functionalizing the dppz on theproperties antineoplastic dppz ligands on the antineoplastic and ligands
Cu-5) on the binding into CT-DNA were evaluated by absorption spectroscopy, fluorescence quenching of the ethidium bromide (EtBr)-DNA adduct, and viscosity measurements

Summary

Introduction

The field of metallodrugs has been under scrutiny since the discovery of the anticancer properties of cis-diamminedichloroplatinum(II) (cisplatin). In the search for new and more effective anticancer drugs, a wide range of transition metal complexes have been synthesized and tested as anticancer agents [5,6]. Pharmaceutics 2021, 13, 764 complexes have been synthesized and tested as anticancer agents [5,6]. Possible candidates copper exmany biological systems and isbiological involved in many biological processes such asbiological energy meists in many systems and is involved in many processes such as energy metabolism and oxygen transportation. In this regard, the interest in copper(I) Copper compounds attractedcompounds special interest as possible because copper[7,8,9,10,11]

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Conclusion