Synthesis And Anticancer Activities Of Biquinazoline Diselenides Compounds

In recent years, the study found that quinazoline-containing compounds hadvarious pharmacological and biological activity, such as anti-inflammatory, antibacterial,anti-HIV, anti-inflammatory, anti-cancer, etc. Quinazoline, as supporting structure,connect different pharmacophore which combined with a variety of biologicalmacromolecules that could produce a variety of biological activity. Especially,quinazoline compounds played an important role in the field of anti-tumor drug research.Most of the enzymes in human body were made up of selenium which is a necessarytrace element in human body to resist disease, anti-aging, enhance the body’s immunefunction to balance the effect of the environment inside the body. Through a variety ofmechanism and multiple target effect, selenium compounds had anticancer activity.Compared with inorganic selenium compunds, organic selenium compounds had higherbioavailability, stronger biological activity, lower toxicity, lower environmentalpollution, etc.In order to create effective antitumor drug, searched new targets for the treatmentof cancer, and guided the development of novel anticancer drugs targets. The thesisused anthranilic acid or substituted anthranilic acid as starting material, after reaction ofclosed-loop, chlorination, and reaction with sodium diselenide, finally synthesizedbiquinazoline diselenides compounds. The structure of the six target products and someintermediates were confirmed by the IR,1H NMR,13C NMR.To investigated the synthetic condition of optimization screening of someintermediates’ synthetic method, especially discussed synthesis routes for6-amino-4(3H)-quinazolinone and4-chloroquinazoline compounds, and made apreliminary probe into the synthesis of1,2-bis[4(3H)-quinazolinone-6-yl]diselane.The novel synthesized compounds against six cancer cell lines (MDA-MB-435,MDA-MB-231, A549, SiHa, Hela and PC-3) were evaluated in vitro. And thebiquinazoline diselenides compounds were contrasted with five commercial anti-cancerdrugs: the Gefitinib, Oxaliplatin, Taxol,10-Hydroxy camptothecin and EpirubicinHydrochloride. The results showed that these synthetic six target products all hadcertain anti-cancer activity. Among them, compounds3a had the most outstandinganti-tumor activity. The inhibition rates of text cancer cells (99.7%,81.6%,93.1%, 99.7%,99.7%and84.5%) were all superior to the anti-cancer drugs Gefitinib andOxaliplatin (10μmol/L).The study chose the MDA-MB-435, A549, SiHa and Hela four tumor cells toconducted cytotoxicity assay, compared with the five kinds of anticancer drugs. Theresults showed that the compound3a and3f treatment group did not cause any other testcell cytotoxic effect (P2>0.05) in addition to3a to MDA-MB-435cells showedcytotoxic (P2<0.05). At the same time, compounds3a and3f treatment group did notcause the cytotoxic effect of other test cells (P2>0.05). So they had potential to becomeantitumor drugs.