Chemoselective Preparation of New Families of Phenolic-Organoselenium Hybrids-A Biological Assessment.

Paloma Begines,José M Padrón,Óscar López,José G Fernández-Bolaños,Inés Maya,Irene Lagunes,Sergio Martos

doi:10.3390/molecules27041315

Paloma Begines, José M Padrón + Show 5 more

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https://doi.org/10.3390/molecules27041315

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Abstract

Being aware of the enormous biological potential of organoselenium and polyphenolic compounds, we have accomplished the preparation of novel hybrids, combining both pharmacophores in order to obtain new antioxidant and antiproliferative agents. Three different families have been accessed in a straightforward and chemoselective fashion: carbohydrate-containing N-acylisoselenoureas, N-arylisoselenocarbamates and N-arylselenocarbamates. The nature of the organoselenium framework, number and position of phenolic hydroxyl groups and substituents on the aromatic scaffolds afforded valuable structure–activity relationships for the biological assays accomplished: antioxidant properties (antiradical activity, DNA-protective effects, Glutathione peroxidase (GPx) mimicry) and antiproliferative activity. Regarding the antioxidant activity, selenocarbamates 24–27 behaved as excellent mimetics of GPx in the substoichiometric elimination of H2O2 as a Reactive Oxygen Species (ROS) model. Isoselenocarbamates and particularly their selenocarbamate isomers exhibited potent antiproliferative activity against non-small lung cell lines (A549, SW1573) in the low micromolar range, with similar potency to that shown by the chemotherapeutic agent cisplatin (cis-diaminodichloroplatin, CDDP) and occasionally with more potency than etoposide (VP-16).

Highlights

Based on the strong antiproliferative features of selenoureas prepared in our group [38,39], we envisioned the possibility of transforming the selenoureido motif into isoselenoureas and analysing the influence of its structure on the biological properties (Figure 1)
We have accomplished the design and chemoselective synthesis of three different families of organoselenium-polyphenolic hybrids with the aim of developing novel antioxidant and antiproliferative agents: carbohydrate-containing N-acyl,Se-phenacyl isoselenoureas, N-aryl,Se-phenacyl isoselenocarbamates and N-aryl,O-phenetyl selenocarbamates. These compounds were subjected to the following biological assays: antiradical (DPPH method), DNA-protective effects, glutathione peroxidase (GPx)-like properties, and antiproliferative assay towards a panel of six human tumour cell lines
The nature of the organoselenium motif, number and position of phenolic hydroxyl groups and substituents on the aromatic scaffolds afforded a series of valuable structure–activity relationships

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Organoselenium derivatives account for one of the most fascinating families of organic compounds. This is due to their high structural diversity [1], and to the plethora of applications of such compounds. Since the isolation of selenoproteins, a subset of more than 20 proteins present in the three domains of life [2], and the consideration of selenium as an essential micronutrient [3], the interest in seleno-derivatives has incessantly increased [4]

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