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

•Schiff base ligand containing ethoxy and bromoethyl group was prepared.•Zn, Cu, and Ni complexes of above Schiff base were synthesized and characterized.•These complexes were able to inhibit topoisomerase I activity and cleave/bind DNA.•These complexes also showed dual actions: anti-proliferation and anti-metastasis.•Cu complex exhibited relatively greater activity than Zn and Ni analogs.

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.

Graphical abstractThese complexes were able to aim multiple targets (inhibit topoisomerase I activity and cleave/bind DNA) and showed dual actions: anti-proliferation and anti-metastasis.Figure optionsDownload full-size imageDownload as PowerPoint slide