N-substitution in isatin thiosemicarbazones decides nuclearity of Cu(II) complexes - Spectroscopic, molecular docking and cytotoxic studies

The mono(1) and bi-nuclear (2) copper(II) complexes containing N-substituted isatin thiosemicarbazone(s) were synthesized, and characterized by analytical and spectroscopic (UV-Visible, FT-IR and EPR) techniques. Bimetallic nature of complex 2 was confirmed by single crystal X-ray crystallography. The structures predicted by spectroscopic and crystallographic methods were validated by computational studies. From the spectroscopic, crystallographic and computational data, the structures were found to be distorted square planar for 1 and distorted square pyramidal for 2. Molecular docking studies showed hydrogen bonding and hydrophobic interactions of the complexes with tyrosinase kinase receptors. Complex 1 exhibited promising cytotoxic activity against Jurkat (leukemia) cell line, and complex 2 displayed more activity against HeLa S3 (cervical) and Jurkat cell lines with the IC50 values of 3.53 and 3.70 mu M, respectively. Cytotoxicity of 1 (Jurkat) and 2 (Jurkat and HeLa S3) was better than that of cisplatin. Morphological changes in A549 (lung), HeLa S3 and Jurkat cell lines were examined in presence of the active complexes with the co-staining of Hoechst, AO (acridine orange) and EB (ethidium bromide) by fluorescence microscope. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Copper(II) complexes containing N-substituted isatin thiosemicarbazone(s) were synthesized and characterized using analytical and spectroscopic techniques. The bimetallic nature of one of the complexes was confirmed by X-ray crystallography. Molecular docking studies revealed interactions with tyrosinase kinase receptors. The cytotoxic activity of the complexes against leukemia and cervical cancer cell lines was found to be promising with better efficacy than cisplatin.