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

Lee SK; Tan KW; Ng SW

doi:10.1016/j.jinorgbio.2016.02.010

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

Lee SK ¹ , Tan KW ² , Ng SW ³

Affiliations

¹ Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
² Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: kongwai@um.edu.my
³ 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

J Inorg Biochem, 2016 06;159:14-21.

PMID: 26901628 DOI: 10.1016/j.jinorgbio.2016.02.010

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.

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