Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

•Selenium-containing quinones were obtained with potent antitumor activity.•Click chemistry was used for the synthesis of selenium-containing quinones.•Mechanistic insights involving NQO1-target were studied.

Selenium-containing quinone-based 1,2,3-triazoles were synthesized using click chemistry, the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition, and evaluated against six types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), PC3 (human prostate cells), SF295 (human glioblastoma cells), MDA-MB-435 (melanoma cells) and OVCAR-8 (human ovarian carcinoma cells). Some compounds showed IC50 values < 0.3 μM. The cytotoxic potential of the quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC), V79 and L929 cells. Mechanistic role for NAD(P)H:Quinone Oxidoreductase 1 (NQO1) was also elucidated. These compounds could provide promising new lead derivatives for more potent anticancer drug development and delivery, and represent one of the most active classes of lapachones reported.

Graphical abstractSelenium-containing quinones were designed and synthesized by click chemistry reaction and evaluated against several human cancer cell lines showing, in some cases, IC50 values below 0.3 μM.Figure optionsDownload full-size imageDownload as PowerPoint slide