Login Register Cart 0
Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Network-Pharmacology and DFT Based Approach Towards Identification of Leads from Homalomena aromatica for Multi-Target In-Silico Screening on Entamoeba histolytica Proteins

Author(s): Ashis Kumar Goswami , Hemanta Kumar Sharma*, Neelutpal Gogoi and Bhaskar Jyoti Gogoi

Volume 15, Issue 3, 2020

Page: [226 - 237] Pages: 12

DOI: 10.2174/1574885514666190801102336

Price: $65

Abstract

Background: Entamoeba histolytica is the primary protozoan that causes amoebic dysentery and is prioritized as the third most prevalent protozoan causing parasitosis. Drug of choice in amoebic dysentery is metronidazole but it has unpleasant side effects with reports of development of resistance in certain cases. Homalomena aromatica Schott. is a plant which is used in different ethnomedicinal practices of South-east Asia to treat stomach ailments against intestinal parasites.

Objective: In the present study, a docking weighted network pharmacology-based approach was employed to understand the effects of a library of 71 natural molecules reported from Homalomena aromatica with reference to four proteins of Entamoeba histolytica namely thioredoxin reductase, cysteine synthase, glyceraldehyde-3-phosphate dehydrogenase, and ornithine decarboxylase.

Methods: Molecular docking of the phytoconstituents of H. aromatica was performed in Biovia Discovery Studio 2017 R2 software suite on the selected proteins of E. histolytica. A connection was established between the proteins and molecules through network pharmacology weighted docking studies with the help of Cytoscape V3.4.0 software to select three molecules namely HM 7, HM 23 and HM 24 on the basis of the generated network between the molecules and targets. Quantum mechanics based Density Functional Theory (DFT) analysis was performed on the filtered molecules to ascertain their viability with respect to LUMO-HOMO orbital energies of the filtered molecules.

Results: On the basis of the docking studies of the natural molecules on the selected protein targets, a network of molecules was built. DFT based minimum energy gap was analysed to further ascertain the most potential inhbitors. Three molecules from H. aromatica; 3,7-dimethylocta-1,6-dien-3- yl acetate, α -methyl-α-(4-methyl-3-pentenyl)-oriranemethanol, and 7-octadiene-2,6-diol-2,6- dimethyl were predicted to be potential lead molecules against amoebiasis.

Conclusion: The present study provides important evidence for the development of new drug molecules to treat amoebiasis.

Keywords: Docking, binding energy, LibDock, linalool, amoebiasis, lipinski`s rule.

« Previous Next »
Graphical Abstract

[1]
Calzada F, Yépez-Mulia L, Aguilar A. In vitro susceptibility of Entamoeba histolytica and Giardia lamblia to plants used in Mexican traditional medicine for the treatment of gastrointestinal disorders. J Ethnopharmacol 2006; 108(3): 367-70.
[http://dx.doi.org/10.1016/j.jep.2006.05.025] [PMID: 16846708]
[2]
López-Camarillo C, López-Rosas I, Ospina-Villa JD, Marchat LA. Deciphering molecular mechanisms of mRNA metabolism in the deep-branching eukaryote Entamoeba histolytica. Wiley Interdiscip Rev RNA 2014; 5(2): 247-62.
[http://dx.doi.org/10.1002/wrna.1205] [PMID: 24249245]
[3]
Bansal D, Sehgal R, Chawla Y, Malla N, Mahajan RC. Multidrug resistance in amoebiasis patients. Indian J Med Res 2006; 124(2): 189-94.
[PMID: 17015933]
[4]
Pinilla AE, López MC, Viasus DF. History of the Entamoeba histolytica protozoan. Rev Med Chil 2008; 136(1): 118-24.
[http://dx.doi.org/10.4067/S0034-98872008000100015] [PMID: 18483662]
[5]
Ximénez C, Morán P, Rojas L, Valadez A, Gómez A. Reassessment of the epidemiology of amebiasis: state of the art. Infect Genet Evol 2009; 9(6): 1023-32.
[http://dx.doi.org/10.1016/j.meegid.2009.06.008] [PMID: 19540361]
[6]
Abhyankar MM, Shrimal S, Gilchrist CA, Bhattacharya A, Petri WA Jr. The Entamoeba histolytica serum-inducible transmembrane kinase EhTMKB1-9 is involved in intestinal amebiasis. Int J Parasitol Drugs Drug Resist 2012; 2: 243-8.
[http://dx.doi.org/10.1016/j.ijpddr.2012.01.002] [PMID: 23267432]
[7]
Phillipson J, Wright C. Antiprotozoal agents from plant sources. Planta Med 1991; 57(S1): S53-9.
[http://dx.doi.org/10.1055/s-2006-960230]
[8]
Babuta M, Bhattacharya S, Bhattacharya A. Protein kinases of the parasitic protist Entamoeba histolyti-ca.Protein phosphorylation in parasites. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co KGaA 2013; pp. 131-54.
[9]
Schlosser S, Leitsch D, Duchêne M. Entamoeba histolytica: identification of thioredoxin-targeted proteins and analysis of serine acetyltransferase-1 as a prototype example. Biochem J 2013; 451(2): 277-88.
[http://dx.doi.org/10.1042/BJ20121798] [PMID: 23398389]
[10]
Bautista E, Calzada F, Ortega A, Yépez-Mulia L. Antiprotozoal activity of flavonoids isolated from Mimosa tenuiflora (Fabaceae-Mimosoideae). Chem Soc 2011; 55(4): 251-3.
[11]
Upcroft P, Upcroft JA. Drug targets and mechanisms of resistance in the anaerobic protozoa. Clin Microbiol Rev 2001; 14(1): 150-64.
[http://dx.doi.org/10.1128/CMR.14.1.150-164.2001] [PMID: 11148007]
[12]
Martínez-Palomo A, Martínez-Báez M. Selective primary health care: strategies for control of disease in the developing world. X. Amebiasis. Rev Infect Dis 1983; 5(6): 1093-102.
[http://dx.doi.org/10.1093/clinids/5.6.1093] [PMID: 6140740]
[13]
Pittman FE, Pittman JC. Amebic liver abscess following metronidazole therapy for amebic colitis. Am J Trop Med Hyg 1974; 23(2): 146-50.
[http://dx.doi.org/10.4269/ajtmh.1974.23.146] [PMID: 4361705]
[14]
Stanley SL Jr. Amoebiasis. Lancet 2003; 361(9362): 1025-34.
[http://dx.doi.org/10.1016/S0140-6736(03)12830-9] [PMID: 12660071]
[15]
Debnath A, Parsonage D, Andrade RM, et al. A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target. Nat Med 2012; 18(6): 956-60.
[http://dx.doi.org/10.1038/nm.2758] [PMID: 22610278]
[16]
Mori M, Jeelani G, Masuda Y, et al. Identification of natural inhibitors of Entamoeba histolytica cysteine synthase from microbial secondary metabolites. Front Microbiol 2015; 6: 962.
[http://dx.doi.org/10.3389/fmicb.2015.00962] [PMID: 26441896]
[17]
Kundu S, Roy D. Computational study of glyceraldehyde-3-phosphate dehydrogenase of Entamoeba histolytica: implications for structure-based drug design. J Biomol Struct Dyn 2007; 25(1): 25-33.
[http://dx.doi.org/10.1080/07391102.2007.10507152] [PMID: 17676935]
[18]
Jhingran A, Padmanabhan PK, Singh S, et al. Characterization of the Entamoeba histolytica ornithine decarboxylase-like enzyme. PLoS Negl Trop Dis 2008; 2(1)e115
[http://dx.doi.org/10.1371/journal.pntd.0000115] [PMID: 18235846]
[19]
Quach J, St-Pierre J, Chadee K. The future for vaccine development against Entamoeba histolytica. Hum Vaccin Immunother 2014; 10(6): 1514-21.
[http://dx.doi.org/10.4161/hv.27796] [PMID: 24504133]
[20]
Miller-Sims VC, Petri WA Jr. Opportunities and obstacles in developing a vaccine for Entamoeba histolytica. Curr Opin Immunol 2002; 14(5): 549-52.
[http://dx.doi.org/10.1016/S0952-7915(02)00372-2] [PMID: 12183151]
[21]
Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br J Pharmacol 2007; 152(1): 9-20.
[http://dx.doi.org/10.1038/sj.bjp.0707305] [PMID: 17549047]
[22]
Kayser O, Kiderlen AF, Croft SL. Natural products as antiparasitic drugs. Parasitol Res 2003; 90(2): S55-62.
[http://dx.doi.org/10.1007/s00436-002-0768-3] [PMID: 12937967]
[23]
Pais-Morales J, Betanzos A, García-Rivera G, Chávez-Munguía B, Shibayama M, Orozco E. Resveratrol induces apoptosis-like death and prevents in vitro and in vivo virulence of Entamoeba histolytica. PLoS One 2016; 11(1)e0146287
[http://dx.doi.org/10.1371/journal.pone.0146287] [PMID: 26731663]
[24]
Barua CC, Talukdar A, Phukan B, Hazarika S, Barua AG, Baishya G. Phytochemical screening and in vitro antioxidant activity of ethanolic extract of Homalomena aromatica (Araceae) root. Der Pharm Lett 2014; 6(1): 128-38.
[25]
Majumdar K, Datta B. A study on ethnomedicinal usage of plants among the folklore herbalists and Tripuri medical practitioners: Part-II. Nat Prod Radiance 2007; 6(1): 66-73.
[26]
Policegoudra RS, Goswami S, Aradhya SM, et al. Bioactive constituents of Homalomena aromatica essential oil and its antifungal activity against dermatophytes and yeasts. J Mycol Med 2012; 22(1): 83-7.
[http://dx.doi.org/10.1016/j.mycmed.2011.10.007] [PMID: 23177818]
[27]
Wintoch H, Morales A, Duque C, Schreier P. (R)-(-)-(E)-2,6-Dimethyl-3,7-octadiene-2,6-diol 6-O-β-d-Glucopyranoside: Natural precursor of hotrienol from lulo fruit (Solanum vestissimum D.) peelings. J Agric Food Chem 1993; 41(8): 1311-4.
[http://dx.doi.org/10.1021/jf00032a028]
[28]
Ilc T, Parage C, Boachon B, Navrot N, Werck-Reichhart D. Monoterpenol oxidative metabolism: Role in plant adaptation and potential applications. Front Plant Sci 2016; 7: 509.
[http://dx.doi.org/10.3389/fpls.2016.00509] [PMID: 27200002]
[29]
Zaks A, Davidovich-Rikanati R, Bar E, Inbar M, Lewinsohn E. Biosynthesis of linalyl acetate and other terpenes in lemon mint (Mentha aquatica var. citrata, Lamiaceae) glandular trichomes. Isr J Plant Sci 2008; 56(3): 233-44.
[http://dx.doi.org/10.1560/IJPS.56.3.233]
[30]
Kehie M, Kehie P, Pfoze NL. Phytochemical and ethnopharmacological overview of endangered Homalomena aromatica Schott : An aromatic medicinal herb of Northeast India. IJNPR 2017; 8(1): 18-31.
[31]
Pradhan S, Sinha C. High throughput screening based highly potent sulfonylbenzamide anti-diabetic drug. Curr Drug Ther 2018; 13(2): 162-73.
[http://dx.doi.org/10.2174/1574885512666171023154352]
[32]
Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 2011; 27(3): 431-2.
[http://dx.doi.org/10.1093/bioinformatics/btq675] [PMID: 21149340]
[33]
Kumar S, Saini V, Maurya IK, et al. Design, synthesis, DFT, docking studies and ADME prediction of some new coumarinyl linked pyrazolylthiazoles: Potential standalone or adjuvant antimicrobial agents. PLoS One 2018; 13(4)e0196016
[http://dx.doi.org/10.1371/journal.pone.0196016] [PMID: 29672633]
[34]
Asati V, Thakur SS, Upmanyu N, Bharti SK. Virtual screening, molecular docking, and DFT studies of some thiazolidine-2,4-diones as potential PIM-1 kinase inhibitors. ChemistrySelect 2018; 3(1): 127-35.
[http://dx.doi.org/10.1002/slct.201702392]
[35]
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]
[36]
Ntie-Kang F. An in silico evaluation of the ADMET profile of the StreptomeDB database. Springerplus 2013; 2(1): 353.
[http://dx.doi.org/10.1186/2193-1801-2-353] [PMID: 23961417]
[37]
Nisha CM, Kumar A, Nair P, et al. Molecular docking and in silico admet study reveals acylguanidine 7a as a potential inhibitor of β -secretase. Adv Bioinformatics 2016; p. 9258578.
[38]
Beena T, Sudha L, Nataraj A, Balachandran V, Kannan D, Ponnuswamy MN. Synthesis, spectroscopic, dielectric, molecular docking and DFT studies of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one: an anticancer agent. Chem Cent J 2017; 11(6): 6.
[http://dx.doi.org/10.1186/s13065-016-0230-8] [PMID: 28119762]
[39]
Qaddir I, Rasool N, Hussain W, Mahmood S. Computer-aided analysis of phytochemicals as potential dengue virus inhibitors based on molecular docking, ADMET and DFT studies. J Vector Borne Dis 2017; 54(3): 255-62.
[http://dx.doi.org/10.4103/0972-9062.217617] [PMID: 29097641]
[40]
Li Y, Evans JNS. The Fukui Function: A key concept linking frontier molecular orbital theory and the hard-soft-acid-base principle. J Am Chem Soc 1995; 117(29): 7756-9.
[http://dx.doi.org/10.1021/ja00134a021]

Rights & Permissions Print Cite
Article Metrics
39
2
1
1
© 2024 Bentham Science Publishers | Privacy Policy