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Current Drug Research Reviews

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ISSN (Print): 2589-9775
ISSN (Online): 2589-9783

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Research Article

In Silico Discovery of Novel Phytoconstituents of Amyris pinnata as a Mitotic Spindle Kinase Inhibitor

Author(s): Ghanshyam R. Parmar*, Ashish P. Shah, Girish U. Sailor and Avinash Kumar Seth

Volume 12, Issue 2, 2020

Page: [175 - 182] Pages: 8

DOI: 10.2174/2589977512666200220122211

Price: $65

Abstract

Background: Despite many successes in the discovery of numerous cancer chemotherapeutic agents from natural sources, some of the moieties were dropped because of its inefficiency or serious toxicity. Mitosis is an ordered series of fundamentally mechanical events in which identical copies of the genome are moved to two discrete locations within the dividing cell. The crucial role of the mitotic spindle in cell division has identified, which is an important target in cancer chemotherapy. In the present study, we are reporting molecular docking studies and in silico pharmacokinetic profiles of selected phytoconstituents obtained from Amyris pinnata.

Methods: Molecular docking studies of selected phytoconstituents were performed using iGEMDOCK. The crystal structure of the protein was exported from the protein data bank (PDB id: 4C4H). In silico pharmacokinetic profile of selected phytoconstituents was performed using the SWISSADME server.

Results: Compound AMNP6 showed higher binding affinity as compared to the standard ligand. All the selected phytoconstituents have passed the Lipinski rule of five and shown no violations.

Conclusion: Good binding affinity and drug likeliness of the AMNP6 suggest that it can be further investigated and explored as mitotic spindle kinase inhibitor in cancer disease.

Keywords: In silico design, molecular docking studies, ADMET prediction, Amyris pinnata, assembly checkpoints, natural medicinal plants.

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[1]
Liu X, Winey M. The MPS1 family of protein kinases. Annu Rev Biochem 2012; 81(1): 561-85.
[http://dx.doi.org/10.1146/annurev-biochem-061611-090435]]
[2]
Xie Y, Wang A, Lin J, et al. Mps1/TTK: a novel target and biomarker for cancer. J Drug Target 2017; 25(2): 112-8.
[3]
Palmer CG, Livengood D, Warren AK, Simpson PJ, Johnson IS. The action of the vincaleukolastine on mitosis in vitro. Exp Cell Res 1960; 20(1): 198-201.
[http://dx.doi.org/10.1016/0014-4827(60)90234-2] [PMID: 14429980]
[4]
Levan A. The effect of colchicine on root mitoses in Allium. Hereditas 1938; 24(4): 471-86.
[http://dx.doi.org/10.1111/j.1601-5223.1938.tb03221.x]
[5]
Farnsworth NR, Akerele O, Bingel AS, Soejarto DD, Guo Z. Medicinal plants in therapy. Bull World Health Organ 1985; 63(6): 965-81.
[PMID: 3879679]
[6]
Cragg GM, Newman DJ, Snader KM. Natural products in drug discovery and development. J Nat Prod 1997; 60(1): 52-60.
[http://dx.doi.org/10.1021/np9604893] [PMID: 9014353]
[7]
Shah AP, Sanghvi KP, Sureja DK, Seth AK. In silico drug design and molecular docking studies of some natural products as tyrosine kinase inhibitors. IJPRT 2017; 5(1): 5-9.
[8]
Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971; 93(9): 2325-7.
[http://dx.doi.org/10.1021/ja00738a045] [PMID: 5553076]
[9]
Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA. Podophyllotoxin: Distribution, sources, applications and new cytotoxic derivatives. Toxicon 2004; 44(4): 441-59.
[http://dx.doi.org/10.1016/j.toxicon.2004.05.008] [PMID: 15302526]
[10]
Damayanthi Y, Lown JW. Podophyllotoxins: Current status and recent developments. Curr Med Chem 1998; 5(3): 205-52.
[PMID: 9562603]
[11]
Badal S, Williams SA, Huang G, et al. Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri. Fitoterapia 2011; 82(2): 230-6.
[http://dx.doi.org/10.1016/j.fitote.2010.10.003] [PMID: 20951188]
[12]
Hasbun C, Calderón M, Romero I. 2, 5-Diaryloxazols and coumarins from roots of Amyris brenesii. Fitoterapia 1990; 61(1)
[13]
Laguna A. Alkaloids and coumarins from the leaves of amyris diatripa. Planta Med 1984; 50(1): 112.
[http://dx.doi.org/10.1055/s-2007-969641] [PMID: 17340271]
[14]
Peng J, Hartley RM, Fest GA, Mooberry SL. Amyrisins A-C, O-prenylated flavonoids from Amyris madrensis. J Nat Prod 2012; 75(3): 494-6.
[http://dx.doi.org/10.1021/np200796e] [PMID: 22260294]
[15]
Hasbun C, Castro O. Coumarins from bark of amyris barbata. J Nat Prod 1986; 49(5): 948-9.
[http://dx.doi.org/10.1021/np50047a044]
[16]
Hernan E, Cordova B, Garelli-M L. New coumarin in Amyris simplicifolia. Phytochemistry 1974; 13758-60.
[17]
Chavarría M, Castro V, Poveda L, Renato M. Cuatro compuestos nuevos del extracto no polar de la planta Amyris brenesii (Rutaceae) de Costa rica. Rev Biol Trop 2008; 56(3): 1043-51.
[PMID: 19419026]
[18]
Badawi MM, Seida AA, Kinghorn AD, Cordell GA, Farnsworth NR. Potential anticancer agents. XVIII. Constituents of Amyris pinnata. J Nat Prod 1981; 44(3): 331-4.
[http://dx.doi.org/10.1021/np50015a016]
[19]
Cuca-Suarez LE, Della-Monache F, Coy-Barrera E. Cytotoxic Constituents from bark and leaves of Amyris pinnata Kunth. Rec Nat Prod 2015; 9(3): 441.
[20]
Goldspiel BR. Clinical overview of the taxanes Pharmacotherapy: JHPDT 1997; 17(5)
[21]
Budman DR. Vinorelbine (Navelbine): A third-generation vinca alkaloid. Cancer Invest 1997; 15(5): 475-90.
[http://dx.doi.org/10.3109/07357909709047587] [PMID: 9316630]
[22]
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46(1-3): 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0 PMID: 11259830]
[23]
Molinspiration Cheminformatics [Internet] Calculation of molecular properties and bioactivity score [cited 2020 Nov 16] Available from: http://www.molinspiration.com/cgi-bin/properties

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