Bioactive half-sandwich Ru(ii) arene imidazolyl-benzylidene phenolate complexes: synthesis, <i>in silico</i> studies and cytotoxicity against HeLa and MCF-7 cells.

Abstract

A series of half-sandwich type Ru(ii) arene complexes [(η6- p -cymene)RuCl(L)] (RuL1-RuL4) have been synthesized and characterized using various spectroscopic techniques such as FT-IR, NMR and ESI-MS. Their interactions with bovine serum albumin (BSA) and calf thymus DNA were studied employing various spectroscopic methods, which revealed significant biomolecular affinity, with RuL2 exhibiting the highest binding constants (2.48 × 105 M-1 for DNA and 0.919 × 106 M-1 for BSA). The molecular docking studies supported the experimental results by elucidating favourable binding modes with both target biomolecules. Furthermore, TD-DFT calculations were carried out to analyze the electronic transitions and molecular properties of the complexes. The antiproliferative activity of these complexes was tested on different human cell lines, including human breast (MCF-7), cervical (HeLa), and non-cancerous human embryonic kidney (HEK-293) cells. Among these, RuL1 = 28.74 ± 0.43 µM and RuL2 = 21.88 ± 1.21 µM showed the highest cytotoxicity with the highest efficacy towards MCF-7 cells over the HeLa cells. Furthermore, RuL1 and RuL2 displayed a very low toxicity on HEK-293 cells, signalling their selectivity. Mechanistic studies revealed that these lead complexes stimulated the generation of intracellular reactive oxygen species (ROS), as confirmed by DCFH-DA staining, and induced apoptosis, as evidenced by acridine orange/ethidium bromide staining. The experimental and theoretical findings show that the half-sandwich Ru(ii) arene imidazolyl-benzylidene phenolate complexes can be utilized to create selective anticancer drugs based on ruthenium.

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