Low-dimensional compounds containing bioactive ligands. Part XVI: Halogenated derivatives of 8-quinolinol N-oxides and their copper(II) complexes

Abstract

Four N-oxides, 8-quinolinol N-oxide (8-HQNO), 5,7-dichloro-8-quinolinol N-oxide (HdClQNO), 5,7-dibromo-8-quinolinol N-oxide (HdBrQNO) and 7-iodo-8-quinolinol N-oxide (HIQNO) as well as their six copper complexes, CuCl2(8-HQNO)2(H2O) (1), CuCl2(HdClQNO)2(H2O)2 (2), Cu(dClQNO)2(CHCl3) (3), Cu(dClQNO)2(H2O) (4), {[Cu(dBrQNO)2]•2H2O}n (5) and CuCl2(HIQNO)2(H2O)4 (6) were synthesised as possible anticancer agents. Crystal structures of N-oxides contain planar molecules held together via hydrogen bonds involving oxygen atoms of N-oxide groups as acceptors. Crystal structure of 5 represents the first structure of a copper(II) complex with an N-oxide ligand derived from 8-HQNO and is formed by infinite chains. In the chain, the Cu(II) atom coordinates to six oxygen atoms from two bidentate chelating dBrQNO ligands occupying apexes of elongated tetragonal bipyramid with bridging oxygen atoms of N-oxide groups in axial positions. Antiproliferative activity of prepared N-oxides as well as their complexes was studied using in vitro MTT assay against the MDA-MB-231, HCT-116 and A549 cancer cell lines and their selectivity was verified on MSCs cells. Among the tested cancer cell lines, A549 and MDA-MB-231 cells were the most sensitive to the tested complexes. Complex 1 showed the highest cytotoxicity against both tumor cell lines. At concentration, which could be tested in animal models, 1 induced cell death in more than 50% of cancer cells and in 20% of MSCs indicating its selectivity.