Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles.

Stephan Mokesch,Michael A Jakupec,Alexander Roller,Matthias H M Klose,Heiko Geisler,Klaudia Cseh,Samuel M Meier-Menches,Bernhard K Keppler,Michaela Hejl,Wolfgang Kandioller

doi:10.3389/fchem.2020.00209

Stephan Mokesch, Michael A Jakupec + Show 8 more

Open Access

https://doi.org/10.3389/fchem.2020.00209

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Abstract

A series of 2-phenylbenzothiazole derivatives and their corresponding organometallic ruthenium(II) and osmium(II) complexes were synthesized, designed to exploit both, the attributes of the half-sandwich transition metal scaffold and the bioactivity spectrum of the applied 2-phenylbenzothiazoles. All synthesized compounds were characterized via standard analytical methods. The obtained organometallics showed antiproliferative activity in the low μM range and are thus at least an order of magnitude more potent than the free ligands. ESI-MS measurements showed that the examined compounds were stable in aqueous solution over 48 h. Additionally, their binding preferences to small biomolecules, their cellular accumulation and capacity of inducing apoptosis/necrosis were investigated. Based on the fluorescence properties of the selected ligand and the corresponding ruthenium complex, their subcellular distribution was studied by fluorescence microscopy, revealing a high degree of colocalization with acidic organelles of cancer cells.

Highlights

The first stepping stone toward the application of coordination compounds for tumor therapy was the discovery of the antiproliferative activity of cisplatin (Rosenberg, 1971, 1973)
The goal of this study was the synthesis of 2phenylbenzothiazole-based Ru(II) and Os(II) piano-stool complexes, investigations on their biological activity profiles, and an attempt to derive preliminary structure-activity relationships
No complex showed any affinity toward Se- and N-donor amino acids

Summary

Introduction

The first stepping stone toward the application of coordination compounds for tumor therapy was the discovery of the antiproliferative activity of cisplatin (Rosenberg, 1971, 1973). The second intensively studied Ru(III) complex is NAMI-A; further clinical investigations have been canceled due to insufficient efficacy (Alessio, 2017). Another class of antitumor ruthenium coordination compounds is represented by half-sandwich complexes with piano-stool geometry. Most of these complexes act as Anticancer Potential of Benzothiazole-Based Metallacycles

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