药物-酶相互作用谱分析环糊精-木犀草素超分子包合性能及理论模建
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摘要
目的采用药物-酶相互作用谱研究β-环糊精(β-cyclodextrin,β-CD)与木犀草素(luteolin,Lut)药物超分子包合作用并比较分析其与经典方法的异同。方法采用光谱实验测定Lut/β-CD-Lut包合物与溶菌酶(lysozyme,LZM)的相互作用,利用Gaussian量化方法计算β-环糊精与Lut的稳定包合构型,计算各构型的总能量。运用分子模建方法探索木犀草素/包合物与溶菌酶相互作用过程中超分子包合物的稳定构型并比较分析其差异性。结果相互作用谱法既能更灵敏地表征包合物的包合性能,又能有效展现LZM输送包合物的机制,分子模拟结果与量化计算结果基本一致,均获得了包合物的最稳定构型。结论相关结果可为研究木犀草素-β-环糊精包合物的药理作用提供实验结果,可为包合物超分子体系的研究方法提供参考。
OBJECTIVE To investigate the supermolecular inclusion properties of beta-cyclodextrin and luteolin by drug-enzyme interaction fluorescence spectra and analyze the similarities and differences between the interaction optical spectroscopy and the classical method. METHODS The total energy of the stable inclusion of cyclodextrin-luteolin was calculated by Gaussian quantitative method,and the stable inclusions in the process of interaction between Lut / inclusion complex and LZM were studied by molecular modeling. RESULTS The fluorescence spectroscopy not only represented the property of the inclusion with higher sensitivity,but also showed the conveying mechanism of LZM to inclusion compound. The molecular modeling showed consistent results with Gaussian quantum calculation; both of the two methods obtained the stable configuration of β-CD-Lut inclusion. CONCLUSION The relevant result provides an experimental consequence for the pharmacology research of beta-cyclodextrin-luteolin inclusion complex and also offers a new reference to the research of supermolecular inclusion compound.
OBJECTIVE To investigate the supermolecular inclusion properties of beta-cyclodextrin and luteolin by drug-enzyme interaction fluorescence spectra and analyze the similarities and differences between the interaction optical spectroscopy and the classical method. METHODS The total energy of the stable inclusion of cyclodextrin-luteolin was calculated by Gaussian quantitative method,and the stable inclusions in the process of interaction between Lut / inclusion complex and LZM were studied by molecular modeling. RESULTS The fluorescence spectroscopy not only represented the property of the inclusion with higher sensitivity,but also showed the conveying mechanism of LZM to inclusion compound. The molecular modeling showed consistent results with Gaussian quantum calculation; both of the two methods obtained the stable configuration of β-CD-Lut inclusion. CONCLUSION The relevant result provides an experimental consequence for the pharmacology research of beta-cyclodextrin-luteolin inclusion complex and also offers a new reference to the research of supermolecular inclusion compound.
引文
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[24]LIU Z,SUN SL,LI F,et al.Determination of DNA using EuPPA as fluorescence probe by time-resolved fluorescence[J].Spectrosc Spect Anal,2009,29(7):1599-1602.
[25]MALLICK A,MAITY S,HALDAR B,et al.Photophysics of 3-acetyl-4-oxo-6,7-dihydro-12H indolo-[2,3-a]quinolizine:Emission from two states[J].Chem Phys Lett,2003,371(3):688-693.
[2]CHEN G S,JIANG M.Cyclodextrin-based inclusion complexation bridging supramolecular chemistry and macromolecular selfassembly[J].Chem Soc Rev,2011,5(40):2254-2266.
[3]LIU Y P,QIN C M,YAN D.Advances in application ofβ-cyclodextin inclusion compound to Chinese materia medica field[J].Chin Tradit Herb Drugs(中草药),2003,7(34):101-104.
[4]VOLOBUEF C,MORAES C M,NUMES S,et al.Sufentanil-2-hydroxypr-opyl-β-cyclodextrin inclusion complex for pain treatment:Physicochemical,cytotoxicity,and pharmacological evaluation[J].J Pharm Sci,2012,101(21):3698-3707.
[5]HARUYASU A,TAKUYA L,TOSHIYUKI K,et al.Unique catalytic effect of a cyclodextrine host on photodimerization of coumarin in nonpolar solvents[J].Tetrahedron Lett,2013,54:688-691.
[6]WANG J,CAO Y,SUN B,et al.Physicochemical and release characterization of garlic oil-β-cyclodextrin inclusion complexes[J].Food Chem,2011,127(4):1680-1685.
[7]LEE Y,HOWARD L R,VILLALON B.Flavonoids and autioxidant activity of fresh pepper(capsicum annuum)cultivars[J].J Food Sci,1995,60(3):483-476.
[8]WANG X K.Natural Pharmaceutical Chemistry(天然药物化学)[M].Beijing:People's Medical Press,1994:272-289.
[9]The Beijing Medical College.The Chemical Components in Chinese Herbal Medicine(中草药成分化学)[M].Beijing:People's Medical Press,1983:369.
[10]LU J J,QI J,ZHU D N,et al.Antioxidant activity and structure-activity relationship of the flavones from the leaves of Aquilaria sinensis[J].Chin J Nat Med(中国天然药物),2008,6(6):456-460.
[11]LIN Q L,MAM H,JIN Y H,et al.Isolation and purification of lysozyme from henegg[J].Food Sci(食品科学),2002,2(23):43-46.
[12]ZHU L L,ZHU M J,YANG Y J.Study on the antibacterial activity of lysozyme hydrolysate[J].Sci Technol Food Ind(食品工业科技),2012,13(33):74-77.
[13]SHARON N.The chemical structure of lysozyme substrates and their cleavage by the enzyme[J].P Roy Soc Lond B Bio,1967,167(1009):402-415.
[14]LAURENTS D V,BALDWIN R L.Characterization of the unfolding pathway of hen egg white lysozyme[J].Biochem,1997,36(6):1496-1504.
[15]ZHANG G W,CHEN X X,GUO J B,et al.Study on the interaction of lysozyme in hesperidin and icariin by spectroscope[J].Spectrosc Spect Anal(光谱学与光谱分析),2009,29(1):184-187.
[16]YANG R,QU L B,CHEN X L,et al.Study on the interaction of lysozyme in naringenin by spectroscope[J].Acta Chim Sin(化学学报),2006,74(13):1349-1354.
[17]YANG R,CHEN X L,LI P,et al.Study on the interaction of lysozyme in three types of flavone by spectroscope[J].Chem J Chin Univ(高等学校化学学报),2006,27(9):1673-1676.
[18]GUO M,YIN X X,CHEN X M,et al.Synthesis of inclusion complex of piperine withβ-cyclodextrin and exploration of the properties of inclusion complex system[J].Chin Pharm J(中国药学杂志),2013,48(21):1841-1846.
[19]JOZSEF S.Cyclodextrin copmplexed generic drugs are generally not bio-equivalent with the reference products:Therefore the increase in number of marketed drug/cyclodextrin formulations is so low[J].J Incl Phenom Macro Chem,2005,52(1):1-11.
[20]ZHANG G M,SHUANG S M,DONG Z M,et al.Investigation on the inclusion behavior of neutral red withβ-cyclodextrin,hydroxyl-propyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin[J].Anal Chim Acta,2002,474:189-195.
[21]ZHANG G M,PANG Y H,SHUANG S M,et al.Spectroseopic studies on the interaction of safranine T with DNA inβ-cyclodextrin and carboxymethy-β-cyclodextrin[J].J Photochem Photobiol,2005,169(1):153-158.
[22]REN X W,WANG Y L,ZHANG S J,et al.Theoretical studies on inclusion complexes of flavonoids withβ-cyclodextrin[J].Chin Tradit Herb Drugs(中草药),2008,39(9):1308-1312.
[23]MA S X.Studies on the inclusion behavior and characterization of three flavonoids with cyclodextrins[D].Kunming:Yunnan University of Nationalities,2009.
[24]LIU Z,SUN SL,LI F,et al.Determination of DNA using EuPPA as fluorescence probe by time-resolved fluorescence[J].Spectrosc Spect Anal,2009,29(7):1599-1602.
[25]MALLICK A,MAITY S,HALDAR B,et al.Photophysics of 3-acetyl-4-oxo-6,7-dihydro-12H indolo-[2,3-a]quinolizine:Emission from two states[J].Chem Phys Lett,2003,371(3):688-693.