Gallium and indium complexes with isoniazid-derived ligands: Interaction with biomolecules and biological activity against cancer cells and Mycobacterium tuberculosis.

Gallium and indium octahedral complexes with isoniazid derivative ligands were successfully prepared. The ligands, isonicotinoyl benzoylacetone (HL) and 4-chlorobenzoylacetone isonicotinoyl hydrazone (HL), and their respective coordination compounds with gallium and indium [GaL(HL)] (GaL), [GaL(HL)] (GaL), [InL(HL)] (InL) and [InL(HL)] (InL) were investigated by NMR, ESI-MS, UV-Vis, IR, single-crystal X-ray diffraction and elemental analysis. In vitro interaction studies with human serum albumin (HSA) evidenced a moderate affinity of all complexes with HSA through spontaneous hydrophobic interactions. The greatest suppression of HSA fluorescence was caused by GaL and InL, which was associated to the higher lipophilicity of HL. In vitro interaction studies with CT-DNA indicated weak interactions of the biomolecule with all complexes. Cytotoxicity assays with MCF-7 (breast carcinoma), PC-3 (prostate carcinoma) and RWPE-1 (healthy human prostate epithelial) cell lines showed that complexes with HL are more active and selective against MCF-7, with the greatest cytotoxicity observed for InL (IC = 10.34 ± 1.69 μM). HL and HL were labelled with gallium-67, and it was verified that GaL has a greater lipophilicity than GaL, as well as higher stability in human serum or in the presence of apo-transferrin. Cellular uptake assays with GaL and GaL evidenced that the HL-containing radiocomplex has a higher accumulation in MCF-7 and PC-3 cells than the non-halogenated congener GaL. The anti-Mycobacterium tuberculosis assays revealed that both ligands and metal complexes are potent growth inhibitors, with MIC (μg mL) values observed from 0.419 ± 0.05 to 1.378 ± 0.21.