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ISSN (Print): 1570-1808
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Research Article

In silico Investigation of Caged Xanthone Compounds Isolated from Cratoxylum sumatranum Stem Bark against Entamoeba histolytica Enzymes

Author(s): Achmad Fuad Hafid*, Defi Kartika Sari, Fendi Yoga Wardana, Mohammad Rizki Fadhil Pratama, Lidya Tumewu, Hilkatul Ilmi, Adita Ayu Permanasari, Hanifah Khairun Nisa and Aty Widyawaruyanti

Volume 21, Issue 12, 2024

Published on: 05 October, 2023

Page: [2423 - 2437] Pages: 15

DOI: 10.2174/1570180820666230818140501

Price: $65

Abstract

Background: Amoebiasis is caused by Entamoeba histolytica, a pathogenic species living on human colon tissues. Metronidazole is currently used for the treatment of amoebiasis, but resistance of E. histolytica to the use of such treatment has been reported. Therefore, the development of new antiamoebic drugs is still very much needed for clinical treatment. Preliminary research on extract and fractions from Cratoxylum sumatranum stem bark has shown their anti-amoebic activity. Two compounds from the cage xanthone groups, cochinchinoxanthone and cochinchinone D, have been isolated from the active fraction of C. sumatranum stem bark.

Objective: This study aimed to investigate the anti-amoebic activity of the two known compounds against E. histolytica.

Methods: The in silico method used was molecular docking with several receptors, including thioredoxin reductase, triose phosphate isomerase, pyruvate ferredoxin oxidoreductase, Giardia fructose-1,6- bisphosphate aldolase, serine acetyltransferase, and phosphoserine phosphatase. The prediction of ADMET properties was also carried out for both the compounds.

Results: The results showed cochinchinone D to have a higher binding affinity to thioredoxin reductase, pyruvate ferredoxin oxidoreductase, and Giardia fructose-1,6-bisphosphate aldolase receptors than cochinchinoxanthone. In contrast, cochinchinoxanthone bound better to the triose phosphate isomerase and phosphoserine phosphatase receptors, while both exhibited the same affinity for serine acetyltransferase. In general, the two compounds were also found to have similar ADMET profiles.

Conclusion: In conclusion, caged xanthone compounds from C. sumatranum have the potential to be developed as anti-amoebic agents against E. histolytica through the mechanism of inhibition of these enzymes.

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[1]
Kantor, M.; Abrantes, A.; Estevez, A.; Schiller, A.; Torrent, J.; Gascon, J.; Hernandez, R.; Ochner, C. Entamoeba histolytica: Updates in clinical manifestation, pathogenesis, and vaccine development. Can. J. Gastroenterol. Hepatol., 2018, 2018, 4601420.
[http://dx.doi.org/10.1155/2018/4601420] [PMID: 30631758]
[2]
Shirley, D.A.T.; Watanabe, K.; Moonah, S. Significance of amebiasis: 10 reasons why neglecting amebiasis might come back to bite us in the gut. PLoS Negl. Trop. Dis., 2019, 13(11), e0007744.
[http://dx.doi.org/10.1371/journal.pntd.0007744] [PMID: 31725715]
[3]
Gonzales, M.L.M.; Dans, L.F.; Sio-Aguilar, J. Antiamoebic drugs for treating amoebic colitis. Cochrane Database Syst. Rev., 2019, 1(1), CD006085.
[PMID: 30624763]
[4]
Shirley, D.A.T.; Farr, L.; Watanabe, K.; Moonah, S. A review of the global burden, new diagnostics, and current therapeutics for amebiasis. Open Forum Infect. Dis., 2018, 5(7), ofy161.
[http://dx.doi.org/10.1093/ofid/ofy161] [PMID: 30046644]
[5]
Debnath, A.; Ndao, M.; Reed, S.L. Reprofiled drug targets ancient protozoans. Gut Microbes, 2013, 4(1), 66-71.
[http://dx.doi.org/10.4161/gmic.22596] [PMID: 23137963]
[6]
Shrivastav, M.T.; Malik, Z. Somlata, Revisiting drug development against the neglected tropical disease, amebiasis. Front. Cell. Infect. Microbiol., 2021, 10, 628257.
[http://dx.doi.org/10.3389/fcimb.2020.628257] [PMID: 33718258]
[7]
Parsonage, D.; Sheng, F.; Hirata, K.; Debnath, A.; McKerrow, J.H.; Reed, S.L.; Abagyan, R.; Poole, L.B.; Podust, L.M. X-ray structures of thioredoxin and thioredoxin reductase from Entamoeba histolytica and prevailing hypothesis of the mechanism of Auranofin action. J. Struct. Biol., 2016, 194(2), 180-190.
[http://dx.doi.org/10.1016/j.jsb.2016.02.015] [PMID: 26876147]
[8]
Rodríguez-Romero, A.; Hernández-Santoyo, A.; del Pozo Yauner, L.; Kornhauser, A.; Fernández-Velasco, D.A. Structure and inactivation of triosephosphate isomerase from Entamoeba histolytica. J. Mol. Biol., 2002, 322(4), 669-675.
[http://dx.doi.org/10.1016/S0022-2836(02)00809-4] [PMID: 12270704]
[9]
Stephen, P.; Vijayan, R.; Bhat, A.; Subbarao, N.; Bamezai, R.N.K. Molecular modeling on pyruvate phosphate dikinase of Entamoeba histolytica and in silico virtual screening for novel inhibitors. J. Comput. Aided Mol. Des., 2008, 22(9), 647-660.
[http://dx.doi.org/10.1007/s10822-007-9130-2] [PMID: 17710553]
[10]
Martínez-Castillo, M.; Pacheco-Yepez, J.; Flores-Huerta, N.; Guzmán-Téllez, P.; Jarillo-Luna, R.A.; Cárdenas-Jaramillo, L.M.; Campos-Rodríguez, R.; Shibayama, M. Flavonoids as a natural treatment against entamoeba histolytica. Front. Cell. Infect. Microbiol., 2018, 8, 209.
[http://dx.doi.org/10.3389/fcimb.2018.00209] [PMID: 29988403]
[11]
Kumar, S.; Raj, I.; Nagpal, I.; Subbarao, N.; Gourinath, S. Structural and biochemical studies of serine acetyltransferase reveal why the parasite Entamoeba histolytica cannot form a cysteine synthase complex. J. Biol. Chem., 2011, 286(14), 12533-12541.
[http://dx.doi.org/10.1074/jbc.M110.197376] [PMID: 21297164]
[12]
Mishra, V.; Ali, V.; Nozaki, T.; Bhakuni, V. Entamoeba histolytica Phosphoserine aminotransferase (EhPSAT): Insights into the structure-function relationship. BMC Res. Notes, 2010, 3(1), 52.
[http://dx.doi.org/10.1186/1756-0500-3-52] [PMID: 20199659]
[13]
Hernández Ceruelos, A.; Romero-Quezada, L.C.; Ruvalcaba Ledezma, J.C.; López Contreras, L. Therapeutic uses of metronidazole and its side effects: An update. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(1), 397-401.
[PMID: 30657582]
[14]
Nguyen, H.D.; Trinh, B.T.D.; Nguyen, N.K.; Dang, S.V.; Pham, H.D.; Nguyen, L.H.D. Xanthones from the twigs of Cratoxylum cochinchinense. Phytochem. Lett., 2011, 4(1), 48-51.
[http://dx.doi.org/10.1016/j.phytol.2010.11.006]
[15]
Sidahmed, H.M.A.; Abdelwahab, S.I.; Mohan, S.; Abdulla, M.A.; Mohamed Elhassan Taha, M.; Hashim, N.M.; Hadi, A.H.A.; Vadivelu, J.; Loke Fai, M.; Rahmani, M.; Yahayu, M. α -Mangostin from Cratoxylum arborescens (Vahl) Blume Demonstrates Anti-Ulcerogenic Property: A Mechanistic Study. Evid. Based Complement. Alternat. Med., 2013, 2013, 1-10.
[http://dx.doi.org/10.1155/2013/450840] [PMID: 23634169]
[16]
Li, Z.P.; Lee, H.H.; Uddin, Z.; Song, Y.H.; Park, K.H. Caged xanthones displaying protein tyrosine phosphatase 1B (PTP1B) inhibition from Cratoxylum cochinchinense. Bioorg. Chem., 2018, 78, 39-45.
[http://dx.doi.org/10.1016/j.bioorg.2018.02.026] [PMID: 29533213]
[17]
Rattanaburi, S.; Daus, M.; Watanapokasin, R.; Mahabusarakam, W. A new bisanthraquinone and cytotoxic xanthones from Cratoxylum cochinchinense. Nat. Prod. Res., 2014, 28(9), 606-610.
[http://dx.doi.org/10.1080/14786419.2014.886212] [PMID: 24571674]
[18]
Ren, Y.; Matthew, S.; Lantvit, D.D.; Ninh, T.N.; Chai, H.; Fuchs, J.R.; Soejarto, D.D.; de Blanco, E.J.C.; Swanson, S.M.; Kinghorn, A.D. Cytotoxic and NF-κB inhibitory constituents of the stems of Cratoxylum cochinchinense and their semisynthetic analogues. J. Nat. Prod., 2011, 74(5), 1117-1125.
[http://dx.doi.org/10.1021/np200051j] [PMID: 21428375]
[19]
Mahabusarakam, W.; Nuangnaowarat, W.; Taylor, W. Xanthone derivatives from cratoxylum cochinchinense roots. Phytochemistry, 2006, 67(5), 470-474.
[http://dx.doi.org/10.1016/j.phytochem.2005.10.008] [PMID: 16310231]
[20]
Wardana, F.Y.; Sari, D.K.; Adianti, M.; Permanasari, A.A.; Tumewu, L.; Nozaki, T.; Widyawaruyanti, A.; Hafid, A.F. Proceedings of BROMO Conference (BROMO 2018), 2018, Jul 11-122018, pp. 77-82.
[21]
Seo, E.K.; Kim, N.C.; Wani, M.C.; Wall, M.E.; Navarro, H.A.; Burgess, J.P.; Kawanishi, K.; Kardono, L.B.S.; Riswan, S.; Rose, W.C.; Fairchild, C.R.; Farnsworth, N.R.; Kinghorn, A.D. Cytotoxic prenylated xanthones and the unusual compounds anthraquinobenzophenones from Cratoxylum sumatranum. J. Nat. Prod., 2002, 65(3), 299-305.
[http://dx.doi.org/10.1021/np010395f] [PMID: 11908969]
[22]
Buana, M.B.B.; Iqbal, M.; Barus, T.F.; Al-Fatony, Z.; Sudrajat, H.; Khairi, S. Isolation and structural elucidation of new xanthone from root bark of Cratoxylum sumatranum. Bot. Res. Int., 2009, 2(4), 233-234.
[23]
Tantapakul, C.; Maneerat, W.; Sripisut, T.; Ritthiwigrom, T.; Andersen, R.J.; Cheng, P.; Cheenpracha, S.; Raksat, A.; Laphookhieo, S. New Benzophenones and Xanthones from Cratoxylum sumatranum ssp. neriifolium and their antibacterial and antioxidant activities. J. Agric. Food Chem., 2016, 64(46), 8755-8762.
[http://dx.doi.org/10.1021/acs.jafc.6b03643] [PMID: 27788582]
[24]
Siswodihardjo, S.; Pratama, M.R.F.; Praditapuspa, E.N.; Kesuma, D.; Poerwono, H.; Widiandani, T. Boesenbergia Pandurata as an anti-breast cancer agent: Molecular docking and ADMET Study. Lett. Drug Des. Discov., 2022, 19(7), 606-626.
[http://dx.doi.org/10.2174/1570180819666211220111245]
[25]
Stork, C.; Chen, Y.; Šícho, M.; Kirchmair, J. Hit Dexter 2.0: Machine-Learning Models for the Prediction of Frequent Hitters. J. Chem. Inf. Model., 2019, 59(3), 1030-1043.
[http://dx.doi.org/10.1021/acs.jcim.8b00677] [PMID: 30624935]
[26]
Wardana, F.Y.; Sari, D.K.; Adianti, M.; Permanasari, A.A.; Tumewu, L.; Nozaki, T.; Widyawaruyanti, A.; Hafid, A.F. In vitro Anti-Amebic activity of cage xanthones from Cratoxylum sumatranum stem bark against entamoeba histolytica. Pharmacogn. J., 2020, 12(3), 452-458.
[http://dx.doi.org/10.5530/pj.2020.12.70]
[27]
Chabrière, E.; Vernède, X.; Guigliarelli, B.; Charon, M.H.; Hatchikian, E.C.; Fontecilla-Camps, J.C. Crystal structure of the free radical intermediate of pyruvate:ferredoxin oxidoreductase. Science, 2001, 294(5551), 2559-2563.
[http://dx.doi.org/10.1126/science.1066198] [PMID: 11752578]
[28]
Galkin, A.; Li, Z.; Li, L.; Kulakova, L.; Pal, L.R.; Dunaway-Mariano, D.; Herzberg, O. Structural insights into the substrate binding and stereoselectivity of giardia fructose-1,6-bisphosphate aldolase. Biochemistry, 2009, 48(14), 3186-3196.
[http://dx.doi.org/10.1021/bi9001166] [PMID: 19236002]
[29]
Pye, V.E.; Tingey, A.P.; Robson, R.L.; Moody, P.C.E. The structure and mechanism of serine acetyltransferase from Escherichia coli. J. Biol. Chem., 2004, 279(39), 40729-40736.
[http://dx.doi.org/10.1074/jbc.M403751200] [PMID: 15231846]
[30]
Kumari, P.; Vijayan, R.; Gourinath, S. Structural analysis of EhPSP in complex with 3-phosphoglyceric acid from Entamoeba histolytica reveals a basis for its lack of phosphoglycerate mutase activity. Int. J. Biol. Macromol., 2021, 178, 1-10.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.02.153] [PMID: 33631257]
[31]
Zinad, D.S.; Mahal, A. A-Qader, A.M.; Siswodihardjo, S.; Pratama, M.R.F.; Mohapatra, R.K. 3d-molecular modeling, antibacterial activity and molecular docking studies of some imidazole derivatives. Egypt. J. Chem., 2021, 64(1), 93-105.
[32]
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(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[33]
Pratama, M.R.F.; Poerwono, H.; Siswodihardjo, S. Introducing a two-dimensional graph of docking score difference vs. similarity of ligand-receptor interactions. Indones. J. Biotechnol., 2021, 26(1), 54-60.
[http://dx.doi.org/10.22146/ijbiotech.62194]
[34]
Pratama, M.R.F.; Poerwono, H.; Siswodiharjo, S. ADMET properties of novel 5- O -benzoylpinostrobin derivatives. J. Basic Clin. Physiol. Pharmacol., 2019, 30(6), 20190251.
[http://dx.doi.org/10.1515/jbcpp-2019-0251] [PMID: 31851612]
[35]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7(1), 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[36]
Pires, D.E.V.; Blundell, T.L.; Ascher, D.B. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J. Med. Chem., 2015, 58(9), 4066-4072.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00104] [PMID: 25860834]
[37]
Banerjee, P.; Eckert, A.O.; Schrey, A.K.; Preissner, R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res., 2018, 46(W1), W257-W263.
[http://dx.doi.org/10.1093/nar/gky318] [PMID: 29718510]
[38]
Sukardiman; Ervina, M.; Fadhil Pratama, M.; Poerwono, H.; Siswodihardjo, S. The coronavirus disease 2019 main protease inhibitor from Andrographis paniculata (Burm.f). Ness. J. Adv. Pharm. Technol. Res., 2020, 11(4), 157-162.
[http://dx.doi.org/10.4103/japtr.JAPTR_84_20] [PMID: 33425697]
[39]
Yazid, M.F.H.A.; Ta, G.C.; Mokhtar, M. Classified chemicals in accordance with the globally harmonized system of classification and labeling of chemicals: Comparison of lists of the european union, japan, malaysia and new zealand. Saf. Health Work, 2020, 11(2), 152-158.
[http://dx.doi.org/10.1016/j.shaw.2020.03.002] [PMID: 32596009]
[40]
Edwards, D.I. Mechanisms of selective toxicity of metronidazole and other nitroimidazole drugs. Sex. Transm. Infect., 1980, 56(5), 285-290.
[http://dx.doi.org/10.1136/sti.56.5.285] [PMID: 7000306]
[41]
Andrade, R.M.; Reed, S.L. New drug target in protozoan parasites: the role of thioredoxin reductase. Front. Microbiol., 2015, 6, 975.
[http://dx.doi.org/10.3389/fmicb.2015.00975] [PMID: 26483758]
[42]
Chen, B.; Greenside, P.; Paik, H.; Sirota, M.; Hadley, D.; Butte, A.J. Relating chemical structure to cellular response: An integrative analysis of gene expression, bioactivity, and structural data across 11,000 Compounds. CPT Pharmacometrics Syst. Pharmacol., 2015, 4(10), 576-584.
[http://dx.doi.org/10.1002/psp4.12009] [PMID: 26535158]
[43]
Du, X.; Li, Y.; Xia, Y.L.; Ai, S.M.; Liang, J.; Sang, P.; Ji, X.L.; Liu, S.Q. Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods. Int. J. Mol. Sci., 2016, 17(2), 144.
[http://dx.doi.org/10.3390/ijms17020144] [PMID: 26821017]
[44]
Davis, A.M.; Riley, R.J. Predictive ADMET studies, the challenges and the opportunities. Curr. Opin. Chem. Biol., 2004, 8(4), 378-386.
[http://dx.doi.org/10.1016/j.cbpa.2004.06.005] [PMID: 15288247]
[45]
Muegge, I.; Heald, S.L.; Brittelli, D. Simple selection criteria for drug-like chemical matter. J. Med. Chem., 2001, 44(12), 1841-1846.
[http://dx.doi.org/10.1021/jm015507e] [PMID: 11384230]
[46]
Benet, L.Z.; Hosey, C.M.; Ursu, O.; Oprea, T.I. BDDCS, the Rule of 5 and drugability. Adv. Drug Deliv. Rev., 2016, 101, 89-98.
[http://dx.doi.org/10.1016/j.addr.2016.05.007] [PMID: 27182629]
[47]
Martin, Y.C. A bioavailability score. J. Med. Chem., 2005, 48(9), 3164-3170.
[http://dx.doi.org/10.1021/jm0492002] [PMID: 15857122]

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