摘要
合成了N-水杨醛腙修饰的11-氮杂青蒿素及去氧类似物.采用紫外、荧光、核磁共振以及分子模拟等技术分析了二聚体(3R,5aS,6R,8aS,9R,12S,12aR)-11-(((E)-2-羟基-5-(4-羟基-3-((E)-(((3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-三甲基-10-氧代十氢-3,12-环氧[1,2]二氧杂[4,3-i]异喹啉-11(12H)-基)亚氨基)甲基)苄基)亚苄基)氨基)-3,6,9-三甲基十氢-3,12-环氧[1,2]二氧杂[4,3-i]异喹啉-10(3H)-酮(3)的优势构像;探索了它与血红素的作用行为;研究了它与杯[4]咔唑的结合、识别及被增溶性能.结果表明,因水杨醛腙键的OH与席夫碱N原子之间的分子内氢键作用,3呈现分子钳状的优势构像,使其得以识别血红素.此外,3可被杯[4]咔唑的疏水空腔封装,且结合作用强(结合常数Ka=2.8×10^5 L·mol^-1),因而其水溶性得以改善,这为今后生物活性测试奠定了基础.
N-Salicylaldehyde hydrazone modified 11-azaartemisinins and their deoxy analogues were designed and synthesized.By using various techniques including UV-vis,fluorescence,NMR as well as molecular modeling,the conformations of(3R,5aS,6R,8aS,9R,12S,12aR)-11-(((E)-2-hydroxy-5-(4-hydroxy-3-((E)-(((3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trimethyl-10-oxodecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-11(12H)-yl)imino)methyl)benzyl)benzylidene)amino)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-10(3H)-one(3)was analyzed,the binding behavior between 3 and hemin was measured,and the solubility-enhancing property of 3 by calix[4]carbazole was evaluated.The results show that the intramolecular hydrogen binding between the N atom of Schiff base in N-salicylaldehyde hydrazone bond and the OH favors the formation of tweezer-like conformation of 3,which enables it to interact with hemin in 1∶1 ratio.Moreover,the poor solubility of 3 in water could be enhanced due to its interaction with calix[4]carbazole,which pave the way for the further evaluation of the bioactivities of 3 in the future.
作者
李四聪
季绍聪
赵亮
廖晓雨
刘传峰
汤浩东
舒正宁
杨鹏
裴月湖
Li Sicong;Ji Shaocong;Zhao Liang;Liao Xiaoyu;Liu Chuanfeng;Tang Haodong;Shu Zhengning;Yang Peng;Pei Yuehu(Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016;School of Traditional Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016)
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2019年第10期2860-2866,共7页
Chinese Journal of Organic Chemistry
基金
辽宁省自然科学基金(No.20180550874)资助项目~~
关键词
大环
分子识别
杯芳烃
咔唑
青蒿素
macrocycle
molecular recognition
carbazole
artemisinin
