Design, synthesis, and antiproliferative investigation of novel quinazolinones incorporating 1,3,4-oxadiazole and 1,2,4-triazole thioether moieties

Abstract

In the current study, a series of 1,3,4-oxadiazole and 1,2,4-triazole derivatives linked to quinazolinone were designed and synthesized by using Phase Transfer Catalysis. The structures of the synthesized compounds were confirmed by their IR, ¹H NMR, ¹³C NMR, and HR-ESI-MS spectroscopic data, and their in vitro antiproliferative activities against A549, Hela, MCF-7 as well as L929 were detected by using CCK-8 assay. The results demonstrated that most of the compounds showed better growth inhibitory effect than 5-FU on A549, Hela, and MCF-7 cell lines. Especially, 2-(5-((3-bromophenyl)thio)-1,3,4-oxadiazole-2-yl)quinazolin-4(3H)-one (8o), 4-amino-5-((4-nitrophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9m) and 2-(4-amino-5-(o-tolylthio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9b) showed good antiproliferative activity against A549 cells with IC₅₀ value of 3.46, 2.96, and 3.44 μM, respectively. 2-(4-Amino-5-((3,5-difluorophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9h) and 4-amino-5-((4-nitrophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9m) had obvious inhibitory effects on Hela cells with IC₅₀ values of 1.76 and 3.91 μM, respectively. 2-(4-Amino-5-((2-chlorophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9i) showed high inhibitory activity against MCF-7 cells with IC₅₀ value of 2.72 μM. Meanwhile, all compounds showed lower cytotoxicity to L929 cells than positive control drug 5-FU. In development, according to the above preliminary observation, these novel quinazolinones incorporating 1,3,4-oxadiazole and 1,2,4-triazole thioether moieties could become potential molecular templates for searching new antitumor agents.