The ability of organoselenium molecules to mimic the activity of the antioxidant selenoenzyme glutathione peroxidase (GPx) allows for their use as antioxidant or prooxidant modulators in several diseases associated with the disruption of the cell redox homeostasis. Current drug design in the field is partially based on specific modifications of the known Se-therapeutics aimed at achieving more selective bioactivity towards particular drug targets, accompanied by low toxicity as the therapeutic window for organoselenium compounds tends to be very narrow. Herein, we present a new group of Se-based antioxidants, structurally derived from the well-known group of GPx mimics—benzisoselenazol-3(2H)-ones. A series of N-substituted unsymmetrical phenylselenides with an o-amido function has been obtained by a newly developed procedure: a copper-catalyzed nucleophilic substitution by a Se-reagent formed in situ from diphenyl diselenide and sodium borohydride. All derivatives were tested as antioxidants and anticancer agents towards breast (MCF-7) and leukemia (HL-60) cancer cell lines. The highest H₂O₂-scavenging potential was observed for N-(3-methylbutyl)-2-(phenylselanyl)benzamide. The best antiproliferative activity was found for (−)-N-(1S,2R,4R)-menthyl-2-(phenylselanyl)benzamide (HL-60) and ((−)-N-(1S,2R,3S,6R)-(2-caranyl))benzamide (MCF-7). The structure–activity correlations, including the differences in reactivity of the obtained phenyl selenides and corresponding benzisoselenazol-3(2H)-ones, were performed.

Quinolinones have been known for a long time as broad-spectrum synthetic antibiotics. More recently, the anticancer potential of this group of compounds has been investigated. Following this direction, we obtained a small library of 3-methylidene-1-sulfonyl-2,3-dihydroquinolin-4(1H)-ones with various substituents at positions 1, 2, 6, and 7 of the quinolinone ring system. The cytotoxic activity of the synthesized analogs was tested in the MTT assay on two cancer cell lines in order to determine the structure–activity relationship. All compounds produced high cytotoxic effects in MCF-7, and even higher in HL-60 cells. 2-Ethyl-3-methylidene-1-phenylsulfonyl-2,3-dihydroquinolin-4(1H)-one, which was over 5-fold more cytotoxic for HL-60 than for normal HUVEC cells, was selected for further tests. This analog was shown to inhibit proliferation and induce DNA damage and apoptosis in HL-60 cells.

Coumarin is a plant-derived compound but as such has no medical uses. Several synthetic coumarin analogs have been shown to possess anti-proliferative activity and to induce apoptosis in cancer cells. Here, we explored DNA damage responses in MCF-7 cells treated with our novel synthetic hybrid compound AD-013, which integrates a coumarin moiety and an α-methylene-δ-lactone motif. The mRNA expression of several genes engaged in DNA-damage-induced responses was assessed by quantitative real-time PCR. The protein levels of a few members of phosphoinositide-3-kinases family (ATM, ATR and DNA-PK) and BRCA1 were assessed by ELISA, while p53 was evaluated by western blot method. AD-013 down-regulated DNA-PK gene expression but increased the level of ATM/ATR and p53. The new analog completely inhibited BRCA1 and greatly decreased the activity of BRCA1 protein, engaged in DNA damage repair. Exposure of MCF-7 cells to a coumarin analog AD-013 led to DNA damage and decreased expression of several repair-associated genes.

One of the main tactics to access C-N bonds from inactivated C-H functionalities is direct transition metal-supported aminations. Due to the often harsh reaction conditions, the current goal in the field is the search for more mild and sustainable transformations. Herein, we present the first solvent-free thermally induced C-N bond formation driven by Au(III) salts. The general structure of the products was confirmed by ¹H, ¹³C, ¹⁵N NMR, TGA-DTA and ATR/FT-IR analysis. Additionally, all derivatives were tested as catalysts in a three-component coupling reaction between phenylacetylene, benzaldehyde and piperidine and as anticancer agents on HL-60 and MCF-7 cell lines.