15种中药生物碱类化合物与4-磺酰基杯[6]芳烃的键合作用评价及其键合体系对HepG2和H9c2细胞增殖的抑制作用考察  

Investigation of Host-guest Complexation Between 4-Sulfonylcalix[6]Arene and 15 Alkaloids from Traditional Chinese Medicines and Inhibitory Effect of Binding System on Proliferation of HepG2 and H9c2 Cells

作　　者：李佳阳 余璇 周振宇 王会敏 王萌[1] LI Jia-yang;YU Xuan;ZHOU Zhen-yu;WANG Hui-min;WANG Meng(State Key Laboratory of Component-based Chinese Medicine,Institute of Traditional Chinese Medicine(TCM),Tianjin University of TCM,Tianjin 301617,China)

机构地区：[1]天津中医药大学中医药研究院,组分中药国家重点实验室,天津301617

出　　处：《中国实验方剂学杂志》2021年第13期119-126,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81873191)。

摘　　要：目的:考察15种中药生物碱类化合物(苦参碱、槐定碱、蝙蝠葛碱、蝙蝠葛苏林碱、奎尼丁、奎宁、野百合碱、长春新碱、钩吻素甲、钩吻素子、粉防己碱、苦豆碱、氧化苦参碱、槐果碱、青藤碱)与4-磺酰基杯[6]芳烃(SCA6)的键合能力,并探究除槐定碱、氧化苦参碱、青藤碱外,其余12种生物碱及其键合体系对HepG2和H9c2细胞生存率的影响。方法:采用荧光竞争滴定法测定生物碱与SCA6的键合常数,利用细胞增殖与活性检测试剂盒-8(CCK-8)法考察生物碱/SCA6键合体系对人肝癌细胞HepG2和鼠源性心肌细胞H9c2增殖的抑制作用。结果:15种中药生物碱类化合物与SCA6均以1∶1比例键合良好(键合常数均>1×10^(5)mol·L^(-1),R2>0.98),其中苦豆碱(喹诺里西啶类生物碱)与SCA6键合能力最强(键合常数20.55×10^(6)mol·L^(-1))。除钩吻素甲、野百合碱、苦参碱和槐果碱外,苦豆碱、粉防己碱、蝙蝠葛碱、蝙蝠葛苏林碱、奎尼丁、奎宁、长春新碱和钩吻素子8种生物碱对HepG2均有较强的体外抗肿瘤作用。除蝙蝠葛苏林碱外,其余11种生物碱与SCA6键合前后对HepG2细胞增殖的抑制作用无明显差异;除钩吻素甲、野百合碱、苦参碱和槐果碱外,其余8种生物碱与SCA6键合前后对H9c2细胞增殖的抑制作用无明显差异。结论:SCA6易与双苄基异喹啉类、喹诺里西啶类、吲哚类生物碱发生键合,显著改善生物碱溶解度且不影响其自身的抗肿瘤作用,可为SCA6构建药物传递体系方面的相关应用提供参考。Objective:To investigate bonding ability between 4-sulfonylcalix[6]arene(SCA6)and15 alkaloids(matrine,allomatrine,dauricine,daurisoline,quinidine,quinine,crotaline,vincristine,gelsemine,koumine,tetrandrine,aloperine,oxymatrine,sophocarpine and sinomenine),and to evaluate viability in vitro of HepG2 and H9c2 cells with 12 alkaloids/SCA6 bonding systems(except allomatrine,oxymatrine,sinomenine).Method:Fluorescence competitive titration was used to determine the binding constants of alkaloids and SCA6,the inhibitory effect of alkaloid/SCA6 complex on proliferation of HepG2 and H9c2 cells was investigated by cell counting kit-8(CCK-8).Result:All the 15 alkaloids had good bonding with SCA6 at the ratio of 1∶1(the binding constants>1×10^(5)mol·L^(-1),R2>0.98),the aloperine(quinolizidine alkaloids)and SCA6 had the biggest binding constant(20.55×10^(6)mol·L^(-1)).In addition to gelsemine,crotaline,matrine and sophocarpine,8 alkaloids(including aloperine,tetrandrine,dauricine,daurisoline,quinidine,quinine,vincristine and koumine)exhibited significant anti-tumor effects on HepG2 cells.Except for daurisoline,the anti-proliferation effect of the other 11 alkaloids before and after binding with SCA6 had no difference in HepG2 cells.In addition to gelsemine,crotaline,matrine and sophocarpine,the anti-proliferation effect of the other 8 alkaloids before and after binding with SCA6 had no difference in H9c2 cells.Conclusion:SCA6 shows intense binding ability with bisbenzylisoquinoline,quinolizidine and indole alkaloids.It can improve the solubility of alkaloids without affecting their anti-tumor activity,which provides a reference for subsequent related applications of SCA6 as a drug delivery carrier.

关 键 词：中药 生物碱 超分子化合物 磺化杯芳烃 抗肿瘤 HepG2细胞 H9C2细胞 

分 类 号：R22[医药卫生—中医基础理论] R857.3[医药卫生—中医学]