利培酮和帕利哌酮抗精神病活性的理论研究
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摘要
采用密度泛函理论和时间分辨密度泛函理论,优化利培酮和帕利哌酮的稳态构型,计算Wiberg键级、紫外-可见分子吸收光谱、分子轨道、Hirshfeld原子电荷、福井函数等,预测利培酮和帕利哌酮的活性点位,解释其药理学行为的化学基础。结果表明帕利哌酮上引入的端羟基可降低临近原子的反应活性,从而减轻其药物副作用。
With the help of DFT and Time-Dependent DFT, the stable structures of Risperidone and Paliperidone were optimized, and then Wiberg bond order, UV-Vis spectra, frontier molecular orbital, atomic charge, etc., were calculated, which can predict the active sites and explain the difference of pharmacological behaviors. The results indicated that the terminal hydroxyl group on Paliperidone can greatly affect the reactivity of adjacent atoms, which can decrease its pharmaceutical side-effect.
With the help of DFT and Time-Dependent DFT, the stable structures of Risperidone and Paliperidone were optimized, and then Wiberg bond order, UV-Vis spectra, frontier molecular orbital, atomic charge, etc., were calculated, which can predict the active sites and explain the difference of pharmacological behaviors. The results indicated that the terminal hydroxyl group on Paliperidone can greatly affect the reactivity of adjacent atoms, which can decrease its pharmaceutical side-effect.
引文
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[2]贺楚梅,阳前军,王珍兰.帕利哌酮与利培酮治疗精神分裂症的临床观察[J].中国药房,2016,27(11):1542-1544.
[3]乔屹,梅轶,盛建华.多巴胺D2受体基因Taq1A多态性与利培酮、帕利哌酮所致高泌乳素血症的关系[J].临床精神医学杂志,2016,26(6):399-401.
[4]孙云峰,应茵,夏仲尼.帕利哌酮与利培酮治疗精神分裂症的疗效和安全性Meta分析[J].中国现代应用药学.2014,31(10):1263-1267.
[5]李良,李建华,杨剑虹,等.帕利哌酮与利培酮对首发男性精神分裂症患者糖脂代谢影响的对照研究[J].中国药学杂志,2013,48(8):649-651.
[6]王来海,张瑞岭,张红星,等.帕利哌酮与利培酮治疗首发精神分裂症的临床疗效与安全性[J].中国医院用药评价与分析,2012,12(8):725-728.
[7]郭琴,祖国平,王亚丽,等.基于密度泛函理论的奥氮平和氯氮平光谱性质和药物活性研究[J].河南科学,2017,35(11):1755-1761.
[8]N.Li,P.Quan,X.Wan,C.Liu,X.Liu,L.Fang.Mechanistic insights of the enhancement effect of sorbitan monooleate on olanzapine transdermal patch both in release and percutaneous absorption processes[J].European Journal of Pharmaceutical Sciences,2017,107:138-147.
[9]K.B.Wiberg.Application of the pople-santry-segal CNDO method to the cyclopropylcarbinyl and cyclobutyl cation and to bicyclobutane[J].Tetrahedron,1968,24(3):1083-1096.
[10]F.L.Hirshfeld.Bonded-atom fragments for describing molecular charge densities[J].Theoretical Chemistry Accounts,1977,44(2),129-138.
[11]徐洋,罗海霞,范强,等.新药萘夫西林药理性质的密度泛函研究[J].当代化工,2015,44(4):699-701.
[12]R.G.Parr,W.Yang.Density functional approach to the frontierelectron theory of chemical reactivity[J].Journal of the America n Chemical Society,1984,106(14):4049-4050.
[13]陈莹,徐抗震,宋纪蓉,等.酚酸抗氧化活性的理论计算[J].食品科学2011,32(9):36-39.