Novel N,N′-Disubstituted Selenoureas as Potential Antioxidant and Cytotoxic Agents

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.

A selenoureido-iminoglycolipid transported by zeolitic-imidazolate framework nanoparticles: a novel antioxidant therapeutic approach

“…Considering the aforementioned in vitro and in vivo therapeutic immunomodulatory properties of DSeU 13 and the well-known role played by the selenoureido motif as ROS scavenging, 32 we selected this bioactive sp 2 -IGL as target candidate to perform the proof-of-concept study. The stereoselective synthesis of (1 S )-( N ′-dodecylselenoureido)-5 N ,6 O -oxomethylidenenojirimycin 13 (DSeU, Fig.…”

Novel Acylselenourea Derivatives: Dual Molecules with Anticancer and Radical Scavenging Activity

“…On the other hand, molecules that exert both antioxidant and antiproliferative activity have been reported, such as 2,6-diaminopyridine derivatives [42], 1,3,5-trisubstituted aryl-5-hydroxypyrazoline analogues [43], 3,5-bis(arylidene)-4-piperidones [44], and several phosphoramidates containing selenium [45]. Most of them display moderate anticancer activity together with excellent antioxidant capacity [11,46,47].…”

Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety

“…Many organoselenium compounds exhibit antioxidant activity closely correlated to their ability to scavenge reactive oxygen species (ROS) [24]. It was recently shown that selenoureas of the similar structures possess moderate antioxidant activity [25]. Thus, at the further steps, the complex investigation of the target compounds' ability to interact with protons, electrons, and radicals was conducted.…”

“…The sample solution (0.1 mL) was mixed with 0.1 mL phosphate buffer (0.2 M, pH 6.6) and 0.1 mL potassium ferricyanide (1%). For each test compound, different concentrations of EtOH were used (5,10,25,50,100,200 and 250 µM). The resulting mixture was incubated at 50 • C for 20 min.…”