Synthesis, spectral characterization and biological evaluation of some copper(II) complexes containing 4-oxo-4H-chromene-3-carbaldehyde-4(N)-substituted thiosemicarbazones

Abstract

Four new water soluble chromone appended copper(II) complexes of the type [Cu(L)Cl] were synthesized from CuCl2·2H2O and 3-formylchromone-4N-substituted thiosemicarbazones (HL1–HL4). Characterization of the compounds was done by using analytical and spectral techniques such as elemental analyses, IR, UV–Visible, EPR and Mass spectrometry, which confirmed their formation. Single crystals suitable for X-ray diffraction were obtained for complex [Cu(L4)Cl], in which the ligand coordinated in a tridentate monobasic ONS donor fashion. The compounds strongly bound to CT-DNA (Calf Thymus DNA) through intercalation. BSA (Bovine Serum Albumin) and HSA (Human Serum Albumin) binding studies were carried out to check the binding ability of the compounds with protein and the mechanism of quenching was found to be static. The occurrence of microenvironmental change in protein was further confirmed by three dimensional (3D) fluorescence experiments. DNA cleavage experiments of the complexes showed that the complexes cleaved supercoiled DNA pBR322 without any external agent. The complexes have shown significant growth inhibitory activity against selected types of bacteria namely S. aureus, S. pneumonia, P. auroginosa, S. paratyphi and fungi namely C. albicans, T. rubrum, A. niger, A. fumigatus and C. tropicalis. Tests on cell proliferation of human lung cancer cell line (A549) and human breast cancer cell line (MCF-7) were performed for all the compounds. The new water soluble complexes overcome cisplatin resistance in the MCF-7 and A549 cell lines. All the compounds were found to be non-toxic against human normal keratinocyte cells (HaCaT). The biological studies indicated that the complex [Cu(L3)Cl] (3) exhibited better activity among the compounds and the complexes exhibited biological activity in the following order [Cu(L3)Cl] (3) > [Cu(L2)Cl] (2) > [Cu(L1)Cl] (1) > [Cu(L4)Cl] (4).