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

Abstract

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.

Anti-tubercular profile of new selenium-menadione conjugates against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain and multidrug-resistant clinical isolates

“…Considering the important chemical interest and potential biological applications of 1,4-naphthoquinones and chalcogen derivatives, different research groups have concentrated their efforts to develop new compounds possessing these two structural moieties [ 31 ]. A method for the synthesis of selenonaphthoquinones ( 2 ) by phenylselenide ions has been reported in the literature by Sakakibara [ 32 ], and others chalcogenium-naphthoquinones were successively explored by Jacob to obtain new redox agents ( 3-5 ) as anti-cancer drugs [ [33] , [34] , [35] , [36] ], as shown in Fig.1 .…”

Crystal structure of 2-(3,5-dimethoxyphenylamino)-3-chloronaphthalene-1,4-dione

“…Dyes are also very important materials [5,6] that most quinones found themselves in [7]. They also display reach biological activities [8] like antifungal [9], antibacterial [10], anticancer [11], antimalarial [12], hypoglycemic [13], analgesic [14], anti-inflammatory [15], and HIV inhibitory [16]. The redox polymers based on quinones owing to their redox ability have been investigated to develop batteries and biosensors [17,18].…”

On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells

“…25,26,33 Compound 6 was prepared from C-allyl lawsone upon reaction with iodine to obtain the cyclized product, which underwent nucleophilic substitution with sodium azide. Finally, the last clickable derivative 7 was obtained from nor-lapachol, previously synthesized from lapachol, by the well-established Hooker oxidation method.…”

“…24b Lapachones exhibit potent antitumor activity due to their ability to act on multiple targets, as we have recently demonstrated. 25 This family of quinoidal derivatives can be divided into α-lapachones (para-quinones) and β-lapachones (orthoquinones). We have demonstrated that both α-and β-lapachones display cytotoxic activity in cancer cells.…”