Synthesis And Biological Activity Of Disulfide Derivatives Based On Quinazolinone

Cancer is considered to be the second most common cause of one of the major causes of death.Quinazolinone derivatives constitute an important class of biologically active compounds.The quinazolinone core is found within both natural products and in pharmaceuticals,representing a privileged scaffold given the range of activities such as antidiabetic,antibacterial,antiinflammatory,anticoagulant,antioxidant,antiproliferative,anticonvulsant,antifibrotic,and antituberculosis.Meanwhile,disulfide derivatives are also known to display a wide spectrum of biological activities because the disulfide group makes up the core structure of numerous biologically active compounds with many types of biological activities including antibacterial,antitumor,antioxidant,and anti-SARS.Consequently,the importance of disulfide derivatives in the fields of medicinal chemistry has received much attention in the past few decades.Based on the above analysis,24 quinazolinone derivatives were designed and synthesized in this paper.The compounds'structures were characterized by ¹³C NMR,¹HNMR,IR and HR-ESI-MS.Using PX-12?1-methylpropyl-2-imidazolyl disulfide?and 5-FU?5-fluorouracil?as positive control drugs,24 compounds were tested against SMMC-7721,Hela,A549 MCF-7 and L929 cells by CCK-8 method.In addition,the antibacterial activity of these compounds against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus.The results showed that all compounds 7a–7h,8a–8h and 9a–9h exhibited antiproliferation with different degrees,and some compounds showed better effects than positive control PX-12 and 5-fluorouracil against different cancer cell lines.Among these compounds,8c and 9f showed significant antiproliferative activity against SMMC-7721 cells with IC₅₀0 values of 2.88 and 2.56?mol/L,respectively.In Hela cells,compounds 9c and 9d showed highly effective biological activity with IC₅₀values of 3.16 and 2.68?mol/L,respectively.Compounds 7a and 9a exhibited good inhibitory effect against A549 cells with IC₅₀0 values of 3.53 and 3.54?mol/L,respectively.In MCF-7 cells,compounds 7e,8e and 9e displayed excellent activity with IC₅₀0 values of 1.26,1.12 and 1.85?mol/L,respectively.Besides,most of the tested compounds showed low cytotoxic effect against the normal cell lines L929.Biological evaluation indicated that all the tested compounds possessed antibacterial activity with certain degrees.From the experimental results,most of the 24 quinazolinone-based disulfide derivatives showed good anti-tumor activity,and all the compounds showed different degrees of antibacterial activity,which laid a foundation for further study on the biological activity of these compounds.