三种肉桂酰胺衍生物的制备及其与人血清白蛋白的结合

基于临床上肉桂酰胺类药物的广泛应用及优异性能,以间羟基肉桂酸为母体,分别与不同氨基酸反应,设计合成了3种未见报道的肉桂酰胺类衍生物,并用MS、IR、1H NMR、13C NMR进行结构表征。采用分子对接技术和荧光光谱法、同步荧光光谱法、紫外-可见光谱法共同研究了3种衍生物分别和人血清白蛋白(HSA)相结合的机理。AutoDock对接显示,这3种衍生物结合在HSA亚结构域ⅡA(即site Ⅰ)的疏水腔内,维系衍生物与HSA的主要作用力为氢键和范德华力,同时还存在着疏水作用。光谱实验结果表明,在体外生理条件下,衍生物都与HSA形成复合物,对HSA内源荧光产生静态猝灭,且对其构象产生影响。根据不同温度下的热力学函数,确定主要作用力均是氢键和范德华力。分子对接与实验获得了一致的结果。

Abstract

Because of the excellent properties and wide applications of cinnamamide medicines in clinic,three m-hydroxycinnamic acid derivatives were designed and synthetised by the reaction of m-hydroxybenzoic acid with different amino acids,respectively. Their structures were characterized by mass spectrometry,infrared spectroscopy,and nuclear magnetic resonance. The interaction mechanism of derivatives and human serum albumin (HSA) were investigated by AutoDock molecular docking,fluorescence spectroscopy and UV-visible absorption spectroscopy. The results of molecular docking represent that derivatives exist in the hydrophobic pocket of subdomainⅡA(site Ⅰ) of HSA. Hydrogen bonds and van der Waals forces are main acting forces and hydrophobic force is just the secondary consideration. The spectra experiment results indicate that the derivatives can form complexes with HSA respectively and strongly quench the intrinsic fluorescence of HSA through static quenching at different temperatures. Meanwhile,the secondary structure of HSA is influenced. The change in enthalpy (ΔH) and entropy (ΔS) suggest that hydrogen bonds and van der Waals forces are main acting forces. The molecular docking data are consistent with experimental results.

参考文献

[1] Xiao J B,Chen T T,Cao H,et al. Molecular property-affinity relationship of flavanoids and flavonoids for HSA in vitro ［J］. Mol. Nutr. Food Res.,2011,55(2): 310-317.

[2] Guo S H,Shi X L,Yang F,et al. Structural basis of transport of lysophospholipids by human serum albumin ［J］. Biochem. J.,2009,423(1): 23-30.

[3] Yang M L,Song Y M,Lu X Q. Preparation,anticoagulant property test and mechanism discussion of water soluble compound of β-cyclodextrin with warfarin/frulic acid ［J］. Chin. J. Anal. Chem.(分析化学),2015,43(6): 836-842 (in Chinese).

[4] Ma J H,Qin D D,Song Y M. Synthesis of superoxide dismutase-like activity of Co(Ⅱ),Ni(Ⅱ) complexes containing aromatic amines and glycylglycine ［J］. Chin. J. Anal. Chem.(分析化学),2015,43(8): 1136-1144 (in Chinese).

[5] Liang J,Feng S L. Interaction between ambroxol hydrochloride and human serum albumin studied by spectroscopic and molecular modeling methods ［J］. Spectrosc. Spect. Anal.(光谱学与光谱分析),2011,31(4): 1020-1024 (in Chinese).

[6] Xin J W,Ma H Y,Yang M. Spectroscopic studies on the interaction between mecobalamin and bovine serum albumin ［J］. Chin. J. Lumin.(发光学报),2012,33(5): 553-557 (in Chinese).

[7] Wu D. Synthesis and Antidepressant Activity of N-(2-hydroxyethyl) Cinnamam Derivatives ［D］. Yanji: Yanbian University,2011 (in Chinese).

[8] Guan L P,Wei C X,Deng X Q,et al. Synthesis and anticonvulsant activity of N-(2-hydroxyethyl) cinnamamide derivatives ［J］. Eur. J. Med. Chem.,2009,44(9): 3654-3657.

[9] Kong J O,Lee S M,Moon Y S,et al. Nematicidal activity of cassia and cinnamon oil compounds and related compounds toward Bursaphelenchus xylophilus (Nematoda: Parasitaphelenchidae) ［J］. J. Nematol.,2007,39(1): 31-36.

[10] Motohashi N,Ashihara Y,Yamagami C,et al. Structure-antimutagenic activity relationships of benzalacetone derivatives against UV-induced mutagenesis in E. coli WP2uvrA and γ-induced mutagenesis in Salmonella typhimurium TA2638 ［J］. Mutat. Res-Fund. Mol. M,2001,474(1-2): 113-120.

[11] Nie W,Luo J G,Wang X B,et al. Synthesis of new α-glucosidase inhibitors based on oleanolic acid incorporating cinnamic amides ［J］. Chem. Pharm. Bull.,2011,59(8): 1051-1056.

[12] Deng X Q,Wu D,Wei C X,et al. Synthesis and antidepressant-like action of N-(2-hydroxyethyl) cinnamamide derivatives in mice ［J］. Med. Chem. Res.,2011,20(8): 1273-1279.

[13] Ronad P M,Hunashal R D,Darbhamalla S,et al. Synthesis and evaluation of anti-inflammatory and analgesic activities of a novel series of substituted-N-(4-methyl- 2-oxo-2H-chromen-7-yl)benzamides ［J］. Arzneim. Forsch.,2008,58(12): 641-646.

[14] Mou L Y,Lin Z Y,Zhu L Y,et al. Synthesis and vasodilative activities of α-phenylcinnamide ［J］. Acta Pharmaceut. Sinica (药学学报),2001,36(7): 502-506 (in Chinese).

[15] Laskowski R A,Swindells M B. LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery ［J］. J. Chem. Inf. Model.,2011,51(10): 2778-2786.

[16] Jiang B L,Hu Y R,Zhao A R,et al. Characterization of taurine and its derivative binding to HSA using calorimetry and docking ［J］. J. Chem. Pharm. Res.,2013,5(12): 1529-1536.

[17] Zaidi N,Ajmal M R,Rabbani G,et al. A comprehensive insight into binding of hippuric acid to human serum albumin: A study to uncover its impaired elimination through hemodialysis ［J］. PLoS One,2013,8(8): e71422.

[18] Bijari N,Shokoohinia Y,Ashrafi-Kooshk M R,et al. Spectroscopic study of interaction between osthole and human serum albumin: Identification of possible binding site of the compound ［J］. J. Lumin.,2013,143: 328-336.

[19] Pacheco M E,Bruzzone L. Synchronous fluorescence spectrometry: Conformational investigation or inner filter effect ［J］. J. Lumin.,2013,137: 138-142.

[20] Li D J,Hong D F,Guo H,et al. Probing the influences of urea on the interaction of sinomenine with human serum albumin by steady-state fluorescence ［J］. J. Photoch. Photobio. B,2012,117: 126-131.

[21] Xie M X,Long M,Liu Y,et al. Characterization of the interaction between human serum albumin and morin ［J］. BBA-Gen. Subjects,2006,1760(8): 1184-1191.

[22] Yan Z Y,Shao X F,Yan L,et al. Interaction between gatifloxacin and bovine serum albumin ［J］. J. Chin. Pharm. Sci.,2005,14(1): 33-37.

[23] Du C R,Luo X,Wei J R,et al. Preparation of (2E)-3-(4′-halophenyl)-prop-2-enoyl sulfachlorpyridazine sodium salts and their interaction with bovine serum albumin by fluorescence spectroscopy ［J］. Chem. Res. Chin. Univ.,2013,29(5): 854-860.

[24] Wang C,Wu Q H,Li C R,et al. Interaction of tetrandrine with human serum albumin: A fluorescence quenching study ［J］. Anal. Sci.,2007,23(4): 429-433.

[25] Zhang Q,Song Y M,Liu J C,et al. Interaction between complexes of transition metal with warfarin and human serum albumin ［J］. Chin. J. Inorg. Chem.(无机化学学报),2011,27(9): 1772-1780 (in Chinese).

[26] Feng X Q,Fu G Q,Li X F,et al. Interaction of rare earth with bovine serum albumin ［J］. Chin. J. Lumin.(发光学报),2011,32(2): 205-209 (in Chinese).

[27] Wu J X,Li M,Liu Z G,et al. Study on interaction of Y3+ and bovine serum albumin by spectrometry ［J］. Chin. J. Lumin.(发光学报),2012,33(10): 1153-1159 (in Chinese).

[28] Wang J,Zheng X F,Cao H Y,et al. Synthesis of 4-thio-5-iodouridine and the interaction between it and human serum albumin ［J］. Chin. J. Lumin.(发光学报),2013,34(3): 361-368 (in Chinese).

[29] Liu Y,Xie M X,Kang J,et al. Studies on the interaction of total saponins of Panax notoginseng and human serum albumin by Fourier transform infrared spectroscopy ［J］. Spectrochim. Acta A,2003,59A(12): 2747-2758.

[30] Luo X,Du C R,Wei J R,et al. Study of the interaction between sodium salts of (2E)-3-(4′-halophenyl)prop-2-enoyl sulfachloropyrazine and bovine serum albumin by fluorescence spectroscopy ［J］. J. Lumin.,2013,28(2): 202-210.

[31] Mandal P,Bardhan M,Ganguly T. A detailed spectroscopic study on the interaction of Rhodamine 6G with human hemoglobin ［J］. J. Photoch. Photobio. B,2010,99(2): 78-86.

[32] Ross P D,Subramanian S. Thermodynamics of protein association reactions: Forces contributing to stability ［J］. Biochemistry,1981,20(11): 3096-3102.

[33] Lloyd J B F. Synchronized excitation of fluorescence emission spectra ［J］. Nat. Phys. Sci.,1971,231(20): 64-65.

[34] Xiao H B,Zhao J H,Yuan H C,et al. Determination of tetracycline content in pork by synchronous fluorescence spectroscopy with CARS method ［J］. Opt. Precision Eng.(光学精密工程),2013,21(10): 2513-2519 (in Chinese).

杜传荣, 逯东伟, 石康, 陈丹丹, 林翠梧. 三种肉桂酰胺衍生物的制备及其与人血清白蛋白的结合[J]. 发光学报, 2015, 36(11): 1342. DU Chuan-rong, LU Dong-wei, SHI Kang, CHEN Dan-dan, LIN Cui-wu. Synthesis of Three Cinnamamide Derivatives and Their Interaction Mechanism with Human Serum Albumin[J]. Chinese Journal of Luminescence, 2015, 36(11): 1342.

三种肉桂酰胺衍生物的制备及其与人血清白蛋白的结合

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