Synthesis And Biological Activity Of A Class Of Pyridyl-containing Quinazolinone Derivatives

The nitrogen heterocyclic compound quinazolinone have broad biological activities,such as anti-tumor,antibacterial,anti-viral,anti-insect,anticonvulsant and anti-diabetes.At present,some quinazolinone compounds have been on the marketed,such as the antitumor drugs Raltitrexed and Nolatriptan;the sedative drug Methaqualone;the muscle relaxant Afloqualone;and the agricultural fungicide Fluquinconazole.Based on the application of quinazolinone derivatives in marketed drugs,designing and synthesizing novel quinazolinone derivatives have promised research prospects.In this paper,a total of 30 quinazolinone derivatives which have not been reported in the literature were synthesized based on 2-chloronicotinic acid or isatoic anhydride.All compounds were identified by ¹H-NMR,¹³C-NMR and HRMS.The antitumor activities of these compounds were evaluated by MTT assay in vitro.The inhibitory activities of these compounds were mainly tested on human non-small cell lung cancer?A549?,human hepatoma cells?SMMC-7721?,and human prostate cancer cells?PC-3?.The results showed that most of the compounds exhibited certain degree of inhibitory activities at the concentration of 10?M;compound I-A18(IC₅₀=12.14?M)showed comparable inhibitory activity to the positive control drug gefitinib(IC₅₀=9.97?M)against A549 cells;compound II-A3(IC₅₀=3.04?M)showed superior inhibitory activity than the positive control drug 5-fluorouracil(IC₅₀=6.48?M)and gefitinib(IC₅₀=35.36?M)against SMMC-7721 cells.Compound I-B6(IC₅₀=14.19?M)showed superior inhibitory activity than the positive control drug5-fluorouracil(IC₅₀=17.98?M)and gefitinib(IC₅₀=33.61?M)against SMMC-7721cells.