Generic placeholder image

当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

吲哚氨基酸生物碱L-Abrine的分离,固态结构测定,计算机模拟和体外抗癌评估

卷 19, 期 9, 2019

页: [707 - 715] 页: 9

弟呕挨: 10.2174/1568009619666190111111937

价格: $65

conference banner
摘要

背景:相思子。 (孟加拉语中的Kunch)广泛分布于热带和亚热带地区。它是一种典型的植物,同时因民间医学及其毒性而广为人知。 目的:对相思子白色变种种子进行植物学研究。 方法:遵循传统的提取,分离,分离和纯化方法。通过各种光谱分析阐明了该结构,并通过X射线晶体学分析确定了该吲哚类生物碱的固态结构。已经研究了L-abrine与十种主要蛋白质的对接相互作用,这些蛋白质负责各种类型的癌症。电脑模拟研究由Schrodinger Maestro,AutoDock4,PyMOL和AutoDock Vina完成。蛋白质结构可从蛋白质数据库下载。磺胺多巴胺B(SRB)比色测定法用于针对四种人类癌细胞系的体外抗癌评估。 结果:从相思子的白色变种种子中分离出了含有吲哚的异常氨基酸生物碱。在计算机对接研究中显示出对四种人类癌细胞系具有显着的抗增殖活性。 结论:X射线晶体学首次证实了含吲哚的生物碱(α-甲基氨基-β-吲哚丙酸,L-abrine)的固态两性离子结构。高度有希望的计算机和体外研究结果表明,L-abrine可能在未来的抗癌药物发现研究中找到其空间。

关键词: 相思子(Abrus precatorius),细胞毒性,生物碱,阿育吠陀,癌症,氨基酸,两性离子。

图形摘要

[1]
Chatterjee, A.; Pakrashi, S.C. The Treatise on Indian Medicinal Plants; Publications and Information Directorate, CSIR: New Delhi, India, 1992, pp. 66-68.
[2]
Attal, A.R.; Otari, K.V.; Shete, R.V.; Upasani, C.D.; Nandgude, T.D. Abrus precatorius Linnaeus. A Phytopharmacological Review. J. Pharm. Res., 2010, 3, 2585-2587.
[3]
Gupta, S.P.; Chhabru, B.S. New triterpenoid glycosides from Abrus prcatorius. J. Indian Chem. Soc., 2012, 89, 675-677.
[4]
Ross, I.A. Medicinal Plants of the World, Vol. 1 (2nd ed); Chemical Constituents, Traditional and Modern Medicinal Uses. , 2003, pp. 15-31.
[5]
Garaniya, N.; Bapodra, A. Ethno botanical and Phytophrmacological potential of Abrus precatorius L.: A review. Asian Pac. J. Trop. Biomed., 2014, 4(Suppl. 1), S27-S34.
[6]
Davis, J.H. Abrus precatorius (rosary pea). The most common lethal plant poison. J. Fla. Med. Assoc., 1978, 65, 188-191.
[7]
Reedman, L.; Shih, R.D.; Hung, O. Survival after an intentional ingestion of crushed Abrus seeds. West. J. Emerg. Med., 2008, 9, 157-159.
[8]
Maiti, P.C.; Mukherjea, S.; Chatterjee, A. Chemical examination of seeds of Abrus precatorius. J. Indian Forensic Sci., 1970, 9, 64-68.
[9]
Johnson, R.C.; Zhou, Y.; Jain, R.; Lemire, S.W.; Fox, S.; Sabourin, P.; Barr, J.R. Quantification of L-abrine in human and rat urine: A biomarker for the toxin abrin. J. Anal. Toxicol., 2009, 33, 77-84.
[10]
Ghatak, N.; Kaul, R. Chemical examination of the seeds of Abrus precatorius. J. Indian Chem. Soc., 1932, 9, 383-387.
[11]
Ghosal, S.; Dutta, S.K. Alkaloids from Abrus precatorius. Phytochemistry, 1971, 10, 195-198.
[12]
Gupta, N.C.; Singh, B.; Bhakuni, D.S. Steroids and triterpenoids from Alangium lamarckii, Allamanda cathartica, Abrus precatorius and Holoptelea integrifolia. Phytochemistry, 1969, 8, 791-792.
[13]
Markham, K.R.; Wallace, J.R.; Niranjan Babu, Y.; Krishna Murthy, V.; Gopala Rao, M. 8-C-Glcusylscutellarein 6,7-dimethyl ether and its 2˝-O-Apioside from Abrus precatorius. Phytochemistry, 1989, 28, 299-301.
[14]
Alessandro, L.; Franco, D. ’ Giovauni Battista, M.; Deise Lia Barros, C.; Ivan Leoncio, D. Abruquinones: new natural isoflavones. Gazz. Chim. Ital., 1979, 109, 9-12.
[15]
Bharadwaj, D.K.; Bisht, M.S.; Mehta, C.K. Flavonoids from Abrus precatorius. Phytochemistry, 1980, 19, 2040-2041.
[16]
Rose, P.W.; Beran, B.; Bi, C.; Bluhm, W.F.; Dimitropoulos, D.; Goodsell, D.S.; Prlic, A.; Quesada, M.; Quinn, G.B.; Westbrook, J.D.; Young, J.; Yukich, B.; Zardecki, C.; Berman, H.M.; Bourne, P.E. The RCSB Protein Data Bank: redesigned web site and web services. Nucleic Acids Res., 2011, 39(Suppl. 1), D392-D401.
[17]
Hnawell, M.D.; Curtis, D.E.; Lonie, D.C.; Vandermeersch, T.; Zurek, E.; Hutchison, G.R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform., 2012, 4, 17.
[18]
Liang, J.; Edelsbrunner, H.; Woodward, C. Anatomy of protein pockets and cavities: measurement of binding site geometry and implications for ligand design. Protein Sci., 1998, 7, 1884-1897.
[19]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30, 2785-2791.
[20]
Seeliger, D.; de Groot, B.L. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J. Comput. Aided Mol. Des., 2010, 24, 417-422.
[21]
Schrödinger Release 2016-4: MS Jaguar, Schrödinger, LLC 2016.New York, USA.
[22]
The PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC. New York, USA, 2015.
[23]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25, 1605-1612.
[24]
Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31, 455-461.
[25]
Haile, J.M. Mol. Dynamics Simulation., 18; , 1992. Wiley New York, USA .
[26]
Vichai, V.; Kirtikara, K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protoc., 2006, 1, 1112-1116.
[27]
WHO cancer, 2018.. Cancer statistics reports from the WHO. http://www.who.int/mediacentre/factsheets/fs297/en/ (accessed on December 14, 2018)
[28]
Singh, P.; Bhardwaj, A. Mechanism of action of key enzymes associated with cancer propagation and their inhibition by various chemotherapeutic agents. Mini Rev. Med. Chem., 2008, 8, 388-398.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy