Synthesis And Bioactivity Of Selenium-containing Quinazoline Derivatives

Among the six-membered nitrogen-containing heterocyclic compounds,quinazoline is widely found in many natural and synthetic pharmaceutical materials.Because these heterocyclic systems have good biological and drug functions such as antihypertensive,anti-tumor,antipyretic,diuretic,analgesics,antibiotics,anti-doping and antidepressants,and are used as vasodilators.In recent years,more and more quinazoline has been used as a drug backbone to produce quinazoline compounds with extensive biological activity,structural type and high medicinal value,and is one of the focuses in current research.Not only that,selenium is one of the essential trace elements in the human body,selenium medicinal research and development has become a hot topic of concern.Organic selenium compounds were found to be effective in anti-inflammatory,antioxidant,cytoprotective,chemoprotective,antidepressant and antimicrobial effects.Because it can be easily absorbed by the human gastrointestinal tract and shows a higher threshold for toxic effects.In order to develop quinazoline drugs with good biological activity,the research group has done a lot of work.Based on the previous research,this paper chooses o-aminobenzoic acid as raw material,selects the trace element selenium as the coordination element,and makes the quinazoline ring and selenium combine organically.A series of selenium-containing quinazoline compounds were designed and synthesized,and their structures were confirmed by IR,1H NMR.To investigated the synthetic conditon of optimization screening of some intermediates synthetic method,especially discussed routes for quinazoline dibasic sodium compounds.In addition,the synthesis of quinazolin-4-selenium sodium was discussed.The activity of the two quinazoline dibromide compounds synthesized in the research group was further studied.The cell apoptosis of A549(non-small cell lung cancer)cells was determined by double labeling flow cytometry(FCM).Through analysis,it showed that the drug is mainly to make the cell cycle in the G1 or S phase to inhibit cell proliferation,and ultimately the cells to apoptosis.After that,we used the growth rate method to test the initial antimicrobial activity of three common plant pathogens of Gibberella zeae,Fusarium oxysporum and Cytospora mandshurica Miura,the results showed that the compounds had certain antibacterial activity,and the inhibition rate of bis(6-chloroquinazolin-4-yl)dibromide on the pathogen of wheat scab was 96.3%,which was much higher than that of the commercial drug(53.68%).Several other substituted di-selenides also have a considerable inhibitory rate with Hymenazole,which is worth further study.The in vitro activity of cancer cell(MDA-MB-231)was tested by MTT colorimetry.The results showed that the inhibitory rate of 6,8-dibromo quinazoline-4-disodium selenium and 6,8-dichloroquinazolin-4-disodium selenium on proliferation of MDA-MB-231 cells was 99.19% and 67.32% at 72 h in vitro at the concentration of 10μM,better than the positive control drug Gefitinib,showing high anti-cancer activity.