title: Copper complexes with phosphonium containing hydrazone ligand: topoisomerase inhibition and cytotoxicity study.
abstract: Four new copper(II) complexes containing phosphonium substituted hydrazone (L) with the formulations [CuL]Cl(3), [Cu(phen)L]Cl(4), [Cu(bpy)L]Cl(5), [Cu(dbpy)L]Cl(6), (where L = doubly deprotonated hydrazone; phen = 1,10'-phenanthroline; bpy = 2,2'-bipyridine; dbpy = 5,5'-dimethyl-2,2'-bipyridine) have been synthesized. The compounds were characterized by elemental analysis, spectroscopic methods and in the case of crystalline products by X-ray crystallography. The cytotoxicity and topoisomerase I (topo I) inhibition activities of these compounds were studied. It is noteworthy that the addition of N,N-ligands to the copper(II) complex lead to the enhancement in the cytotoxicity of the compounds, especially against human prostate adenocarcinoma cell line (PC-3). Complex 4 exhibits the highest activity against PC-3 with the IC₅₀ value of 3.2 μΜ. The complexes can also inhibit topo I through the binding to DNA and the enzyme.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Shin Thung
authors.initials: ST
authors.lastname: Chew
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kong Mun
authors.initials: KM
authors.lastname: Lo
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sze Koon
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Mok Piew
authors.initials: MP
authors.lastname: Heng
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Wuen Yew
authors.initials: WY
authors.lastname: Teoh
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kae Shin
authors.initials: KS
authors.lastname: Sim
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kong Wai
authors.initials: KW
authors.lastname: Tan
mesh_terms: D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006835:Hydrazones / Q000737:chemistry* / Q000494:pharmacology*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010758:Phosphorus / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D059004:Topoisomerase I Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D006835:Hydrazones; D008024:Ligands; D059004:Topoisomerase I Inhibitors; D010758:Phosphorus; D003300:Copper
keywords: Copper(II) complexes; Cytotoxicity; Hydrazones; Topoisomerase I inhibitor