Synthesis, characterization and biological evaluation of cationic hydrazone copper complexes with diverse diimine co-ligands

Four new copper(ii) complexes containing triphenylphosphonium conjugated salicylaldehyde-(4-fluorobenzhydrazone), (L) with the formulation [CuL]Cl(1), [Cu(phen)L]Cl(2), [Cu(bpy)L]Cl(3), [Cu(dmbpy)L]Cl(4), (where L = doubly deprotonated hydrazone; phen = 1,10'-phenanthroline; bpy = 2,2'-bip...

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Bibliographic Details
Published in:RSC advances 2014-01, Vol.4 (106), p.61232-61247
Main Authors: Chew, Shin Thung, Lo, Kong Mun, Sinniah, Saravana Kumar, Sim, Kae Shin, Tan, Kong Wai
Format: Article
Language:English
Subjects:
Binding
Cationic
Cleavage
Coordination compounds
Copper
Deoxyribonucleic acid
Enzymes
Hydrazones
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Summary:Four new copper(ii) complexes containing triphenylphosphonium conjugated salicylaldehyde-(4-fluorobenzhydrazone), (L) with the formulation [CuL]Cl(1), [Cu(phen)L]Cl(2), [Cu(bpy)L]Cl(3), [Cu(dmbpy)L]Cl(4), (where L = doubly deprotonated hydrazone; phen = 1,10'-phenanthroline; bpy = 2,2'-bipyridine; dmbpy = 5,5'-dimethyl-2,2'-bipyridine) have been synthesized. The compounds were characterized by spectroscopic methods and, in the case of crystalline products, by X-ray crystallography. The topoisomerase I (topo I) inhibition, DNA binding and cleavage activities and cytotoxicity of the compounds were studied. A DNA relaxation study demonstrated that all the copper complexes successfully inhibit topo I enzyme by binding to topo I as the preferred pathway. Complex 1 is the most active with starting inhibitory concentration approximately 20 mu M. The planarity of the tridentate hydrazone Schiff base ligand and the diimine co-ligands increase the binding affinity to DNA. The presence of the 1,10'-phenanthroline co-ligand in complex 2 induces plasmid DNA (pBR322) cleavage without exogenous agents. It is noteworthy that the addition of diimine co-ligands to the copper(ii) complex enhanced the cytotoxicity of the compounds, especially against the human prostate adenocarcinoma cell line (PC-3). Complex 2 exhibits the highest activity against PC-3 with the IC sub(50) value of 2.47 plus or minus 0.37 mu M. Annexin V/propidium iodide analysis showed that compound 1 induces apoptotic and necrotic cell death, whereas compound 2-4 work mainly through apoptosis.
ISSN:2046-2069
2046-2069
DOI:10.1039/C4RA11716F