DNA interactions, antitubercular and cytotoxic activity of heteroleptic CuII complexes containing 1,10-phenanthroline

•Four heteroleptic CuII complexes with 1,10-phenanthroline were prepared.•Such complexes were more cytotoxic than corresponding free ligands and carboplatin.•These complexes efficiently bind to ct-DNA with kb values in the range of 103 M‒1.•Additionally, these CuII complexes exhibited potent antimycobacterial activity. Herein, we describe the synthesis and characterization of novel heteroleptic copper(II) complexes, [Cu(2-HNA)(phen)ClO4]•1•5H2O I, [Cu(6-HNA)(phen)ClO4]•H2O II, [Cu(QNA)(phen)ClO4]•0•5H2O III and [Cu(2-MNA)(phen)ClO4]•0•5H2O IV, where 2-HNA = 2-hydroxynicotinic acid, 6-HNA = 6-hydroxynicotinic acid, QNA = 2-quinolinecarboxylic acid, 2-MNA = 2-mercaptonicotinic acid and phen = 1,10-phenanthroline. The spectral data indicate a square-pyramidal geometry around the copper(II) ion in the solid state, with an acid derivative and 1,10-phenanthroline (N–N) acting as bidentate ligands. A perchlorate ion in the apical position completes the metal coordination sphere. All these complexes exhibited potent activity against the Mycobacterium tuberculosis H37Rv strain, with MIC values in the range of few µM. The cytotoxic activity of these compounds was also investigated toward tumor cell lines (MDA-MB-231 and MCF-7) and in a non-tumorigenic cell line (MCF-10A). Complex I was the most active (IC50 = 4.2 μM) and selective (SI > 3) toward MDA-MB-231 cells. DNA binding studies performed by circular dichroism (CD) and UV–Vis spectroscopic methods, using a Hoechst 33258 displacement assay, indicated that these complexes can efficiently bind to ct-DNA, with Kb values in the range of 103 M‒1. [Display omitted]