Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole.

Robert Czarnomysy,Justyna Magdalena Hermanowicz,Anna Bielawska,Izabela Prokop,Anna Muszyńska,Krzysztof Bielawski,Dominika Radomska

doi:10.3390/molecules25122860

Robert Czarnomysy, Justyna Magdalena Hermanowicz + Show 5 more

Open Access

https://doi.org/10.3390/molecules25122860

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Abstract

Novel transition metal complexes (Au, Pd, Pt) with berenil and 2-(1-methyl-5-nitroimidazol-2-yl)ethanol were obtained through two-step synthesis. The cytotoxicity assay against MCF-7 and MDA-MB-231 breast cancer cells revealed that novel platinum and palladium complexes cause a reduction on the viability of MCF-7 and MDA-MB-231 breast cancer cells to a greater extent than cisplatin. The complexes showed lower cytotoxicity on normal MCF-10A human breast epithelial cells than on tumor cells. Furthermore, we observed that these complexes selectively concentrate in tumor cell mitochondria due to the characteristic for these cells increased membrane potential that may explain their increased proapoptotic activity. The activity of the synthesized compounds against topoisomerase type IIα and their increased impact on DNA defragmentation also were documented. The novel complexes also induced autophagosome changes and inhibited tumor growth in xenograft models (established using breast cancer cells).

Highlights

Despite the development of thousands of anticancer structures, cancer is still a major cause of death worldwide [1]
Since it is known that berenil, has functional and triazene groups, it may bind to metals as linear monodentate, chelating bidentate, and in bridging bidentate modes, we performed IR, 1 H, and 13 C-NMR spectra of the synthesized compounds to determine the mode of metal-berenil bonding
The cytotoxicity assay against breast cancer cells MCF-7 and MDA-MB-231 revealed that the novel compounds were more effective than the hitherto used agent, cisplatin

Summary

Introduction

Despite the development of thousands of anticancer structures, cancer is still a major cause of death worldwide [1]. The main problem in the treatment of cancer is drug resistance from long-term treatment and the adverse side effects of the drugs along with non-specific toxicity [1,2]. The reported new anticancer compounds usually suffer from low stability under physiological conditions, interfering with delivery to the tumor tissues and often resulting in toxic side effects [3]. Metal complexes offer unique characteristics and exceptional versatility, with the ability to alter their pharmacology through facile modifications of geometry and coordination number. This has prompted the search for metal-based complexes with distinctly different structural motifs and non-covalent modes of binding with a primary aim of circumventing current clinical limitations [4]

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