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Current Cancer Drug Targets

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

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Research Article

Isolation, Solid-state Structure Determination, In Silico and In Vitro Anticancer Evaluation of an Indole Amino Acid Alkaloid L-Abrine

Author(s): Subrata Laskar*, Omar Espino and Debasish Bandyopadhyay*

Volume 19, Issue 9, 2019

Page: [707 - 715] Pages: 9

DOI: 10.2174/1568009619666190111111937

Price: $65

Abstract

Background: Abrus precatorius Linn. (Kunch in Bengali) is widely spread in tropical and sub-tropical regions. It is a typical plant species which is well-known simultaneously as folk medicine and for its toxicity.

Objective: Phytoceutical investigation of the white variety seeds of Abrus precatorius Linn.

Methods: Traditional extraction, separation, isolation, and purification processes were followed. The structure was elucidated by various spectral analyses and the solid-state structure of this indolealkaloid was determined by X-ray crystallographic analysis. Docking interactions of L-abrine had been studied against ten major proteins, responsible for various types of cancers. In silico studies were done by Schrödinger Maestro, AutoDock4, PyMOL and AutoDock Vina. The protein structures were downloaded from Protein Data Bank. Sulforhodamine B (SRB) colorimetric assay was used for in vitro anticancer evaluation against four human cancer cell lines.

Results: An indole-containing unusual amino acid alkaloid had been isolated from the white variety seeds of Abrus precatorius Linn. In silico docking studies demonstrated significant antiproliferative activity against four human cancer cell lines.

Conclusion: The solid-state zwitterion structure of the indole-containing alkaloid (α-methylamino- β-indolepropionic acid, L-abrine) has been confirmed for the first time by X-ray crystallography. Highly promising in silico and in vitro results indicate that L-abrine may find its space in future anticancer drug discovery research.

Keywords: Abrus precatorius, cytotoxicity, alkaloid, ayurveda, cancer, amino acid, zwitterions.

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[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.

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