新型α-氨基硫色满酮膦酸酯衍生物的设计、合成及抗炎活性评价  

Design,synthesis and anti-inflammatory activity evaluation of novelα-aminophosphonates bearing thiochromanone

作　　者：王欢 柳如萍 田佳 李思宇 张国平 WANG Huan;LIU Ru-ping;TIAN Jia;LI Si-yu;ZHANG Guo-ping(College of Chemistry and Material Science,Huaibei Normal University,Huaibei 235000,China;Key Laboratory of G reen and Precise Synthetic Chemistry and Applications,Ministry of Education,Huaibei Normal University,Huaibei 235000,China)

机构地区：[1]淮北师范大学化学与材料科学学院,安徽淮北235000 [2]淮北师范大学绿色和精准合成化学及应用教育部重点实验室,安徽淮北235000

出　　处：《中国药物化学杂志》2023年第12期887-893,共7页Chinese Journal of Medicinal Chemistry

基　　金：安徽省教育厅重点项目(2022AH050394);淮北师范大学校级重点实验室开放项目(2022sykf035)。

摘　　要：目的设计合成一系列新型α-氨基硫色满酮膦酸酯衍生物,并进行体外抗炎活性研究。方法以含有不同取代基的苯硫酚和3-氯丙酸为起始原料,经取代、Friedel-Crafts酰基化环合、Claisen缩合、Kabachnik-Fields反应得到目标化合物,并分别采用MTT法和Griess法测定细胞毒性及体外抗炎活性。结果与结论共合成了7个新化合物,其结构均经^(1)H-NMR、^(13)C-NMR和HR-ESI-MS确证。细胞毒性实验结果表明,目标化合物安全性较好。体外抗炎活性实验结果表明,目标化合物对LPS诱导的RAW264.7细胞中炎症因子一氧化氮的释放具有显著抑制作用,其中,化合物4b、4e~4g的抗炎活性远高于阳性对照吲哚美辛。通过机制学研究发现化合物4f可以抑制iNOS和COX-2炎性蛋白的表达从而发挥抗炎活性。本研究可为抗炎小分子药物的设计和开发提供参考。Derivatives of aminophosphonate and thiochromanone have been reported to exhibit diverse biological activities,mainly including anti-tumor and anti-inflammatory activities.To develop novel anti-inflammatory agents,this study hybridized two skeletons,amniophosphonate and thiochromanone.Therefore,sevenα-aminophosphonates bearing thiochromanone were synthesized by substitution,Friedel-Crafts acylation,Claisen condensation and Kabachnik-Fields reaction.The structures of target compounds were characterized by ^(1)H-NMR,^(13)C-NMR and HR-ESI-MS.Cytotoxicity of the target compounds was detected by MTT assay,and their antiinflammatory activity were evaluated using RAW264.7 cell by Griess method.These results showed that the target compounds were safe and compounds 4b,4e-4g exhibited better activities than that of the control agent indomethacin.The further study indicated that compound 4f can suppress the expression of iNOS and COX-2 inflammatory proteins,thereby exerting anti-inflammatory activity.

关 键 词：Α-氨基膦酸酯 硫色满酮 合成 杂化 抗炎活性 炎性蛋白 

分 类 号：R914[医药卫生—药物化学]