海洋来源Neolamellarin A类似物的神经保护活性
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摘要
目的生物碱是自然界中普遍存在的一类含氮的碱性有机化合物,其中海洋生物碱因具有广泛的生物活性而受到极大关注。Neolamellarin A是1种来源于海洋动物海绵并具有新颖吡咯类骨架的生物碱。目前对Neolamellarin A类生物碱的研究探索刚刚起步,希望可以通过更多的活性研究对其加以全面的开发。方法采用细胞毒活性检测(MTT法)及神经细胞保护模型对五个新颖Neolamellarin A的3,4二芳基取代全甲基化类似物进行检测。结果发现该类3,4二芳基取代全甲基化的Neolamellarin A类似物较弱的细胞毒活性和突出的神经保护活性。结论实验结果扩展了该类Neolamellarin A类似物潜在的应用方向并丰富了海洋生物碱的生物功能。
Objective Alkaloids are a class of nitrogenous compounds found in nature.Marine alkaloids deserve great attention with widespread biological activities.Neolamellarin A is a kind of marine alkaloids,possessing bisaryl-pyrrole structural features.There is limited understanding of the biological activity of Neolamellarin class A alkaloids and the exploration of novel biological activity of these compounds is imperative.Methods The 3,4-bisaryl-N-alkylated permethylated analogues of Neolamellarin A were tested by cytotoxic activity assay(MTT)and PC12 neuron-like cell model.Results It was found that the 3,4-bisaryl-N-alkylated permethylated analogues of Neolamellarin A had weaker cytotoxic activity and prominent neuroprotective activity.Conclusion The neuroprotective activities extend the potential application of Neolamellarin A analogues and enrich the biological functions of the marine alkaloids.
Objective Alkaloids are a class of nitrogenous compounds found in nature.Marine alkaloids deserve great attention with widespread biological activities.Neolamellarin A is a kind of marine alkaloids,possessing bisaryl-pyrrole structural features.There is limited understanding of the biological activity of Neolamellarin class A alkaloids and the exploration of novel biological activity of these compounds is imperative.Methods The 3,4-bisaryl-N-alkylated permethylated analogues of Neolamellarin A were tested by cytotoxic activity assay(MTT)and PC12 neuron-like cell model.Results It was found that the 3,4-bisaryl-N-alkylated permethylated analogues of Neolamellarin A had weaker cytotoxic activity and prominent neuroprotective activity.Conclusion The neuroprotective activities extend the potential application of Neolamellarin A analogues and enrich the biological functions of the marine alkaloids.
引文
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[2]Rane R,Sahu N,Shah C,et al.Marine bromopyrrole alkaloids:synthesis and diverse medicinal applications[J].Curr Top Med Chem,2014,14(2):253-273.
[3]Franca P H,Barbosa D P,Da S D,et al.Indole alkaloids from marine sources as potential leads against infectious diseases[J].Biomed Res Int,2014,2014:375423.
[4]Amat M,Perez M,Ballette R,et al.The alkaloids of the madangamine group[J].Alkaloids Chem Biol,2015,74:159-199.
[5]Menna M.Important classes of bioactive alkaloids from marine ascidians:structures,isolation and bioactivity[J].Curr Top Med Chem,2014,14(2):207-223.
[6]Ashok P,Lathiya H,Murugesan S.Manzamine alkaloids as antileishmanial agents:A review[J].Eur J Med Chem,2015,97:928-936.
[7]Nijampatnam B,Dutta S,Velu S E.Recent advances in isolation,synthesis,and evaluation of bioactivities of bispyrroloquinone alkaloids of marine origin[J].Chin J Nat Med,2015,13(8):561-577.
[8]Bailly C.Lamellarins:A tribe of bioactive marine natural products.Outstanding Marine Molecules[M].Wiley-VCH Verlag GmbH&Co.KGaA,2014:377-386.
[9]Fan H,Peng J,Hamann M T,et al.ChemInform abstract:Lamellarins and related pyrrole-derived Alkaloids from marine organisms[J].Chem Rew,2008,39(18):264-287.
[10]Jia A F W L.Recent progress in the research on lamellarins and related pyrrole-derived alkaloids from marine organisms[J].J Chin Pharmaceutical Sciences,2011,20(5):M0005.
[11]Wang X,Ma Z,Wang X,et al.Dimeric pyrrole-imidazole alkaloids:synthetic approaches and biosynthetic hypotheses[J].Chem Commun(Camb),2014,50(63):8628-8639.
[12]Imaoka T,Iwata M,Akimoto T,et al.Synthetic approaches to tetracyclic pyrrole imidazole marine alkaloids[J].Nat Prod Commun,2013,8(7):961-964.
[13]Al-Mourabit A,Zancanella M A,Tilvi S,et al.Biosynthesis,asymmetric synthesis,and pharmacology,including cellular targets,of the pyrrole-2-aminoimidazole marine alkaloids[J].Nat Prod Rep,2011,28(7):1229-1260.
[14]Deslandes S,Chassaing S,Delfourne E.Marine pyrrolocarbazoles and analogues:synthesis and kinase inhibition[J].Mar Drugs,2009,7(4):754-786.
[15]Gjorgjieva M,Masic L P,Kikelj D.Antibacterial and Antibiofilm Potentials of Marine Pyrrole-2-aminoimidazole Alkaloids and Their Synthetic Analogs[J].Mini Rev Med Chem,2016,18(17):13-14.
[16]Soenen D R,Hwang I,Hedrick M P,et al.Multidrug resistance reversal activity of key ningalin analogues[J].Bioorg Med Chem Lett,2003,13(10):1777-1781.
[17]Hamasaki A,Zimpleman J M,Hwang I,et al.Total synthesis of ningalin D[J].J Am Chem Soc,2005,127(30):10767-10770.
[18]Liu R,Liu Y,Zhou Y D,et al.Molecular-targeted antitumor agents.15.Neolamellarins from the marine sponge Dendrilla nigra inhibit hypoxia-inducible factor-1activation and secreted vascular endothelial growth factor production in breast tumor cells[J].J Nat Prod,2007,70(11):1741-1745.
[19]Arafeh K M,Ullah N.Synthesis of Neolamellarin A,an inhibitor of hypoxia-inducible factor-1[J].Nat Prod Commun,2009,4(7):925-926.
[20]Rajasekar S,Anbarasan P.Rhodium-catalyzed transannulation of 1,2,3-triazoles to polysubstituted pyrroles[J].J Org Chem,2014,79(17):8428-8434.
[21]Yin R,Jiang L,Wan S,et al.Efficient syntheses of permethylated derivatives of Neolamellarin A,apyrrolic marine natural product[J].J Ocean Univ Chin,2015,14(2):329-334.
[22]Qiu P,Xu L,Gao L,et al.Exploring pyrimidine-substituted curcumin analogues:Design,synthesis and effects on EGFR signaling[J].Bioorgan Med Chem,2013,21(17):5012-5020.
[23]Yin R,Zhang M,Hao C,et al.Different cytotoxicities and cellular localizations of novel quindoline derivatives with or without boronic acid modifications in cancer cells[J].Chem Comm,2013,49(76):8516-8518.
[24]He Y,Lan Y,Liu Y,et al.Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway[J].Molecules,2016,21(7):862.
[25]Tong S,Zhang M,Wang S,et al.Isothiouronium modification empowers pyrimidine-substituted curcumin analogs potent cytotoxicity and Golgi localization[J].Eur J Med Chem,2016,123:849-857.
[26]Mosmann T.Rapid colorimetric assay for cellular growth and survival:application to proliferation and cytotoxicity assays[J].J Immunol Methods,1983,65(1/2):55-63.
[27]Hao C,Gao L,Zhang Y,et al.Acetylated chitosan oligosaccharides act as antagonists against glutamate-induced PC12cell death via Bcl-2/Bax signal pathway[J].Marine Drugs,2015,13(3):1267-1289.