野黄芩素类似物的设计合成与活性评价  

Design Synthesis and Bioactivity Evaluation of Scutellarein Derivatives

作　　者：袁雅婷 吴秀兰 汤凡 王富江 葛海涛 YUAN Yating;WU Xiulan;TANG Fan;WANG Fujiang;GE Haitao(College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210046,China;Suzhong Pharmaceutical Research Institute Co.,Ltd.,Nanjing 210031,China)

机构地区：[1]南京中医药大学药学院,南京210046 [2]江苏苏中药业研究院有限公司,南京210031

出　　处：《中国药学杂志》2024年第17期1597-1604,共8页Chinese Pharmaceutical Journal

基　　金：泰州市“凤城英才计划”青年科技人才托举工程项目资助(TZ-018);南京中医药大学自然科学基金项目资助(XZR2020099)。

摘　　要：目的合成野黄芩素类似物并对其进行溶解性与生物活性研究。方法基于先导化合物野黄芩素,通过官能团修饰、电子等排原理、母核开环进行结构设计并合成了12个化合物,通过氢核磁共振(1H nuclear magnetic resonance,1H-NMR)、碳核磁共振(13C nuclear magnetic resonance,13C-NMR)和质谱(mass spectrometry,MS)对化合物结构进行表征;测定化合物溶解度并通过钙流检测评价所有化合物对瞬时受体电位离子通道香草素亚家族3(transient receptor potential vanilloid 3,TRPV3)的抑制活性;通过建立咪喹莫特(IMQ)诱导银屑病动物模型,选择3种最具潜力的化合物进行的抗银屑病实验。结果所有化合物溶解度均高于野黄芩素。在钙流实验中,化合物I-01,I-04,I-06显示出较强的TRPV3抑制作用,均优于YHQ,其中,I-06活性最强。银屑病动物实验显示I-06可显著改善银屑病小鼠的病理外观,降低炎症因子IL-6与TNF-α水平,I-06抗银屑病活性最佳,优于I-01、I-04。结论该类野黄芩素类似物对银屑病具有潜在的治疗价值,同时,为靶向TRPV3治疗各种皮肤疾病提供了一个新的思路。OBJECTIVE To synthesize scutellarein derivatives and study their solubility and bioactivity.METHODS Based on the lead compound scutellarein,12 compounds were designed and synthesized using functional group substitution,parent nucleus ring opening,and electron rearrangement principles.The structures of the compounds were characterized through 1H-NMR,13C-NMR and MS,their solubility was tested,and their transient receptor potential vanilloid 3(TRPV3)inhibitory activities were evaluated through calcium flow detection.An animal model of psoriasis induced by imiquimod(IMQ)was established and the three most active compounds were selected for anti-psoriasis evaluation.RESULTS All compounds had higher solubility than scutellarein.In the calcium flow experiment,compounds I-01,I-04,and I-06 showed stronger TRPV3 inhibition than scutellarein,with I-06 having the strongest activity.Animal experiments on psoriasis showed that I-01,I-04,and I-06 could significantly improve the pathological appearance and inflammatory response of psoriasis mice,and I-06 performed the best.CONCLUSION This type of modified scutellarein has potential therapeutic value for psoriasis and provides a new approach for targeting TRPV3 to treat various skin diseases.

关 键 词：野黄芩素类似物 瞬时受体电位离子通道香草素亚家族3 合成 生物活性 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]