Abstract
A series of 30 novel N,N disubstituted selenoureas were synthesized, characterized, and their antioxidant ability was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assays. Additionally, their cytotoxic activity was tested in vitro in a panel of three different cancer (breast, lung and colon) and two normal cell lines. Each selenourea entity contains a para-substituted phenyl ring with different electron-withdrawing and electron-donating groups, and different aliphatic and aromatic nuclei. All of the synthesized selenoureas present antioxidant capacity at high concentrations in the DPPH assay, and three of them (2b, 2c and 2d) showed greater radical scavenging capacity than ascorbic acid at lower concentrations. These results were confirmed by the ABTS assay, where these novel selenoureas present even higher antioxidant capacity than the reference compound Trolox. On the other hand, 10 selenoureas present IC50 values below 10 µM in at least one cancer cell line, resulting in the adamantyl nucleus (6a–6e), the most interesting in terms of activity and selectivity. Outstanding results were found for selenourea 6c, tested in the NCI60 cell line panel and showing an average GI50 of 1.49 µM for the 60 cell lines, and LC50 values ranging from 9.33 µM to 4.27 µM against 10 of these cancer cell lines. To gain insight into its anticancer activity mechanism, we investigated the cell cycle progression of the promising compound 6c, as well as the type of programmed-cell death in a colon cancer cell line it provokes (HT-29). Compound 6c provoked S phase cell cycle arrest and the induction of cell death was independent of caspase activation, suggesting autophagy, though this assertion requires additional studies. Overall, we envision that this compound can be further developed for the potential treatment of colon cancer.
Highlights
Cancer is a group of complex and multifactorial diseases and is considered the third leading cause of death globally
A volume of 100 μL from a previously prepared stock solution of DPPH (100 μM) in methanol were added to 100 μL of the methanolic selenoureas solutions prepared previously, and the antioxidant activity these compounds was assessed by its ability to decolorize DPPH
As a part of our project aiming for the synthesis of organoselenium-based chemotherapeutic agents, we present the synthesis of a novel family of 30 new selenoureas 1–6a–e, following the methodology represented in Scheme 1
Summary
Cancer is a group of complex and multifactorial diseases and is considered the third leading cause of death globally. Sodium selenite exhibited excellent activity in the prevention [7] activity and treatthe prevention andoftreatment of different types of cancers, while other forms, derivatives ment of different[7]. Types cancers, while other derivatives with other chemical such with other chemical forms, such as sodium selenate, did not exert these properties [8]. In addiour research team has reported the preparation and cytotoxic and antioxidant activities acfor tion, our research team has reported the preparation and cytotoxic and antioxidant different selenourea derivatives [21,22,23,24]. We pursue the development of new molecules, the compounds presented in this paper.
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