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Design,Synthesis and Bioactivity Study of marine alkaloid Neobacillamide-A Derivatives

Journal of Ocean University of China 2023年第3期22卷 790-800页

作者： WANG Jiali LI Maowei ZHANG Xiao ZHANG Zhijin LIU Yang LIU Lu YIN Ruijuan JIANG Tao Key Laboratory of marine Drugs Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China marine Biomedical Research Institute of Qiangdao Qingdao 266237China Laboratory for marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China

The Janus kinases(JAKs)are a family of intracellular tyrosine kinases that play an essential role in many basic biological processes,such as apoptosis and *** any dysfunction of the proteins in this pathway may lead to a variety of diseases,including cancer and diseases that affect the immune system,such as severe combined immune deficient(SCID).marine biological resources have become an important source in new drug research and development due to their diversity,complexity and *** this study,marine alkaloid Neobacillamide A was isolated from the greedy and stubborn sponge symbiotic Bacillus atrophicus C89 in the South China *** 24 novel marine alkaloid Neobacillamide A derivatives were designed and synthesized,which were evaluated for their inhibitory activity against JAK/STAT signaling pathway and their cytotoxicity to A549 *** 13c,13o,14d,14g and 14h showed potent JAK/STAT inhibition capability(concentration of 25μmol L^(-1),all inhibitory potencies were above 60%),especially compound 14g exhibited superior JAK/STAT inhibition effect(89.70%inhibition).In addition,all these compounds with a concentration of 25μmol L^(-1)displayed weak or no cytotoxicity to A549 cells,which means that these Neobacillamide A derivatives with JAK/STAT inhibition capability may have potential anti-inflammatory function.

关键词： marine alkaloid Neobacillamide A synthesis JAK/STAT cytotoxicity

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