Synthesis And Biological Activity Of Quinazolinone Derivatives Containing Hydrazone Structural Units

Cancer has always been a hot research direction.The decline in the effect of anti-cancer drugs due to the drug resistance of cancer cells is one of the main problems faced by chemotherapy.In addition,the long-term use of chemical drugs has certain side effects,such as uremia,neurotoxicity and liver toxicity.The development of new high-efficiency and low-toxicity drugs and small molecules is imminent.The structure of quinazolinone has been a research hotspot due to its wide range of biological activities,such as antimalarial,antimicrobial,anti-inflammatory,anticonvulsant,and antihypertensive.The hydrazone structure has been used in anti-tumor,anti-bacterial and anti-viral drugs due to its diverse coordination structure and target binding mode.In this study,a series of derivatives were synthesized by introducing a hydrazone structure into the 2 and 3 positions of the quinazolinone nucleus,and tested their biological activity.Bioactivity assays indicated that these compounds showed good antitumour activitiestowards human lung cancer cells（A549）and human prostate cancer cells（PC-3）and no apparenttoxicity towards those nontumorigenic rat renal tubular epithelial cells（NRK-52E）.In particular,compound D32 showed potent inhibitory activity towards A549 and PC-3 with IC₅₀of7.36 and 7.73μM.Subsequently,the relationships between the compound structures and numerous biologicalactivities are discussed.A good predictive three-dimensional quantitative structure–activity relationship（3D-QSAR）model was constructed via Co MFA to direct the future structural units.The preliminary antibacterial activity results showed that the compounds exhibited a certain inhibitory activity against Xanthomonas oryzae pv.oryzae（Xoo）,Pseudomonas syringae pv.actinidiae（Psa）and Xanthomonas axonopodis pv.citri（Xac）.Among them,D18,D12 and D16,displayed better antibacterial activity against Xoo,Xac and Psa than the control drug Bismerthiazol and Thiediazole-copper respectively.The compound D5 displayed fine broad-spectrum antimicrobial activity against Xoo,Xac and Psa.