title: Topoisomerase I inhibition and DNA cleavage by zinc, copper, and nickel derivatives of 2-[2-bromoethyliminomethyl]-4-[ethoxymethyl]phenol complexes exhibiting anti-proliferation and anti-metastasis activity.
abstract: Three transition metal derivatives (Zn, Cu, and Ni) of 2-[2-bromoethyliminomethyl]-4-[ethoxymethyl]phenol (L) were synthesized by the reaction of the metal salts with the Schiff base ligand in one pot. In the crystal structure of [Zn(L)Br], the Schiff base ligand binds to the metal center through its phenolate oxygen and imine nitrogen, and adopts a distorted tetrahedral geometry. These compounds were found to inhibit topoisomerase I (topo I) activity, induce DNA cleavage and show DNA binding activity. Moreover, these compounds were found to be cytotoxic towards several cancer cell lines (A2780, MCF-7, HT29, HepG2, A549, PC3, LNCaP) and prevent metastasis of PC3. Collectively, Cu(II) complex 2 shows superior activity relative to its Zn(II) and Ni(II) analogs.
authors.affiliation: Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sze Koon
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: kongwai@um.edu.my.
authors.forename: Kong Wai
authors.initials: KW
authors.lastname: Tan
authors.affiliation: Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia; Chemistry Department, Faculty of Science, King Abdulaziz University, P. O box 80203, Jeddah, Saudi Arabia.
authors.forename: Seik Weng
authors.initials: SW
authors.lastname: Ng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D004269:DNA, Bacterial / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009532:Nickel / Q000737:chemistry / Q000494:pharmacology; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D009942:Organometallic Compounds; D059004:Topoisomerase I Inhibitors; D003300:Copper; D009532:Nickel; D015032:Zinc
keywords: Copper; DNA; Nickel; Schiff base; Topoisomerase; Zinc