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Current Drug Discovery Technologies

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ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

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Research Article

A Computational Approach to Investigate the HDAC6 and HDAC10 Binding Propensity of Psidium guajava-derived Compounds as Potential Anticancer Agents

Author(s): Kayode Ezekiel Adewole* and Ahmed Adebayo Ishola

Volume 18, Issue 3, 2021

Published on: 01 May, 2020

Page: [423 - 436] Pages: 14

DOI: 10.2174/1568009620666200502013657

Price: $65

Abstract

Background: Different parts of Psidium guajava are consumed as food and used for medicinal purposes around the world. Although studies have reported their antiproliferative effects via different biochemical mechanisms, their modulatory effects on epigenetic modification of DNA molecules via histone deacetylases (HDACs) are largely unknown.

Objective: This study was carried out to investigate the histone deacetylase 6 (HDAC6) and histone deacetylase 10 (HDAC10) binding propensity of guava-derived compounds, using in silico methods, in other to identify compounds with HDAC inhibitory potentials.

Methods: Fifty-nine guava-derived compounds and apicidin, a standard HDAC inhibitor, were docked with HDAC6 and HDAC10 using AutodockVina after modeling (SWISS-MODEL server) and validating (ERRAT and VERIFY-3D) the structure of HDAC10. Molecular interactions between the ligands and the HDACs were viewed with Discovery Studio Visualizer. Prediction of binding sites, surface structural pockets, active sites, area, shape and volume of every pocket and internal cavities of proteins was done using Computed Atlas of Surface Topography of proteins (CASTp) server, while absorption, distribution, metabolism, and excretion (ADME) study of notable compounds was done using Swiss online ADME web tool.

Results: 2α-hydroxyursolic acid, asiatic acid, betulinic acid, crategolic acid, guajadial A and B, guavacoumaric acid, guavanoic acid, ilelatifol D, isoneriucoumaric acid, jacoumaric acid, oleanolic acid, psiguadial A, B, and C demonstrated maximum interaction with the selected HDACs. ADME studies revealed that although isoneriucoumaric and jacoumaric acid ranked very high as HDAC inhibitors, they both violated the Lipinski’s rule of 5.

Conclusion: This study identified 13 drugable guava-derived compounds that can be enlisted for further studies as potential HDAC6 and HDAC10 inhibitors.

Keywords: Psidium guajava, Histone deacetylase, Histone deacetylase inhibitor, Binding affinity, Epigenetic modification, ADME web tool

Graphical Abstract

[1]
Salazar DM, Melgarejo P, Martínez R, Martínez JJ, Hernández F, Burguera M. Phenological stages of the guava tree (Psidium guajava L.). Sci Hortic (Amsterdam) 2006; 108: 157-61.
[http://dx.doi.org/10.1016/j.scienta.2006.01.022]
[2]
Ashraf A, Sarfraz RA, Rashid MA, Mahmood A, Shahid M, Noor N. Anticancer and cytotoxic effects of Psidium guajava leaf extracts 2016; 0209.
[3]
Ryu NH, Park KR, Kim SM, et al. A hexane fraction of guava Leaves (Psidium guajava L.) induces anticancer activity by suppressing AKT/mammalian target of rapamycin/ribosomal p70 S6 kinase in human prostate cancer cells. J Med Food 2012; 15(3): 231-41.
[http://dx.doi.org/10.1089/jmf.2011.1701] [PMID: 22280146]
[4]
Díaz-de-Cerio E, Verardo V, Gómez-Caravaca AM, Fernández-Gutiérrez A, Segura-Carretero A. Health Effects of Psidium guajava L. Leaves: An Overview of the Last Decade. Int J Mol Sci 2017; 18(4): 897.
[http://dx.doi.org/10.3390/ijms18040897] [PMID: 28441777]
[5]
Bontempo P, Doto A, Miceli M, Mita L, Benedetti R, Nebbioso A, et al. Psidium guajava L . anti-neoplastic effects : induction of apoptosis and cell differentiation 2012; 22-31.
[6]
Kaileh M, Vanden Berghe W, Boone E, Essawi T, Haegeman G. Screening of indigenous Palestinian medicinal plants for potential anti-inflammatory and cytotoxic activity. J Ethnopharmacol 2007; 113(3): 510-6.
[http://dx.doi.org/10.1016/j.jep.2007.07.008] [PMID: 17716845]
[7]
Peng CC, Peng CH, Chen K-C, Hsieh CL, Peng RY. The Aqueous Soluble Polyphenolic Fraction of Psidium guajava Leaves Exhibits Potent Anti-Angiogenesis and Anti-Migration Actions on DU145 Cells. Evid Based Complement Alternat Med 2011.2011219069
[http://dx.doi.org/10.1093/ecam/neq005] [PMID: 21799674]
[8]
Corrêa M, Couto J, Teodoro A. Anticancer properties of Psidium guajava - a mini-review. Asian Pacific Organ Cancer Prev [Internet] 2016; 17: 4199-204. [Available from: http://journal.waocp.org/article_38733.html
[9]
Ganai SA. Novel approaches towards designing of isoform-selective inhibitors against class ii histone deacetylases: The acute requirement for targetted anticancer therapy. Curr Top Med Chem 2016; 16(22): 2441-52.
[http://dx.doi.org/10.2174/1568026616666160212122609] [PMID: 26873193]
[10]
Halkidou K, Gaughan L, Cook S, Leung HY, Neal DE, Robson CN. Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. Prostate 2004; 59(2): 177-89.
[http://dx.doi.org/10.1002/pros.20022] [PMID: 15042618]
[11]
Zhang Z, Yamashita H, Toyama T, et al. HDAC6 expression is correlated with better survival in breast cancer. Clin Cancer Res 2004; 10(20): 6962-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-0455] [PMID: 15501975]
[12]
Wilson AJ, Byun DS, Popova N, et al. Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem 2006; 281(19): 13548-58.
[http://dx.doi.org/10.1074/jbc.M510023200] [PMID: 16533812]
[13]
Ganai SA, Farooq Z, Banday S, Altaf M. In silico approaches for investigating the binding propensity of apigenin and luteolin against class I HDAC isoforms. Future Med Chem 2018; 10(16): 1925-45.
[http://dx.doi.org/10.4155/fmc-2018-0020] [PMID: 29992822]
[14]
Bae HJ, Jung KH, Eun JW, et al. MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer. J Hepatol 2015; 63(2): 408-19.
[http://dx.doi.org/10.1016/j.jhep.2015.03.019] [PMID: 25817558]
[15]
Haakenson J, Zhang X. HDAC6 and ovarian cancer. Int J Mol Sci 2013; 14(5): 9514-35.
[http://dx.doi.org/10.3390/ijms14059514] [PMID: 23644884]
[16]
Li T, Zhang C, Hassan S, Liu X, Song F, Chen K, et al. Histone deacetylase 6 in cancer. J Hematol Oncol 2018; 11: 1-10.
[http://dx.doi.org/10.1186/s13045-018-0654-9]
[17]
Garcia-Manero G, Sekeres MA, Egyed M, et al. A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ⩽30% blasts. Leukemia 2017; 31(12): 2799-806.
[http://dx.doi.org/10.1038/leu.2017.159] [PMID: 28546581]
[18]
Haggarty SJ, Koeller KM, Wong JC, Grozinger CM, Schreiber SL. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA 2003; 100(8): 4389-94.
[http://dx.doi.org/10.1073/pnas.0430973100] [PMID: 12677000]
[19]
Yee AJ, Bensinger WI, Supko JG, et al. Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial. Lancet Oncol 2016; 17(11): 1569-78.
[http://dx.doi.org/10.1016/S1470-2045(16)30375-8] [PMID: 27646843]
[20]
Kolbinger FR, Koeneke E, Ridinger J, et al. The HDAC6/8/10 inhibitor TH34 induces DNA damage-mediated cell death in human high-grade neuroblastoma cell lines. Arch Toxicol 2018; 92(8): 2649-64.
[http://dx.doi.org/10.1007/s00204-018-2234-8] [PMID: 29947893]
[21]
Uba AI, Yelekçi K. Carboxylic acid derivatives display potential selectivity for human histone deacetylase 6: Structure-based virtual screening, molecular docking and dynamics simulation studies. Comput Biol Chem 2018; 75: 131-42.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.05.004] [PMID: 29859380]
[22]
Biasini M, Bienert S, Waterhouse A, et al. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 2014; 42(Web Server issue): W252-8.
[http://dx.doi.org/10.1093/nar/gku340] [PMID: 24782522]
[23]
Bordoli L, Kiefer F, Arnold K, Benkert P, Battey J, Schwede T. Protein structure homology modeling using SWISS-MODEL workspace. Nat Protoc 2009; 4(1): 1-13.
[http://dx.doi.org/10.1038/nprot.2008.197] [PMID: 19131951]
[24]
Benkert P, Künzli M, Schwede T. QMEAN server for protein model quality estimation. Nucleic Acids Res 2009; 37(Web Server issue): W510-4.
[http://dx.doi.org/10.1093/nar/gkp322] [PMID: 19429685]
[25]
Benkert P, Tosatto SCE, Schomburg D. QMEAN: A comprehensive scoring function for model quality assessment. Proteins 2008; 71(1): 261-77.
[http://dx.doi.org/10.1002/prot.21715] [PMID: 17932912]
[26]
Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Cryst 1993.
[http://dx.doi.org/10.1107/S0021889892009944]
[27]
Colovos C, Yeates TO. Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Sci 1993; 2(9): 1511-9.
[http://dx.doi.org/10.1002/pro.5560020916] [PMID: 8401235]
[28]
Bowie JU, Lüthy R, Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional stucture. Science (80-) 1991.
[29]
Lüthy R, Bowie JU, Eisenberg D. Assessment of protein models with three-dimensional profiles. Nature 1992; 356(6364): 83-5.
[http://dx.doi.org/10.1038/356083a0] [PMID: 1538787]
[30]
Van Gunsteren WF, Billeter SR, Eising AA, Hunenberger PH, Krüger P, Mark AE, et al. The GROMOS96 manual and user guide 1996.
[31]
O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform 2011; 3: 33.
[http://dx.doi.org/10.1186/1758-2946-3-33] [PMID: 21982300]
[32]
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31(2): 455-61.
[PMID: 19499576]
[33]
Sánchez-Linares I, Pérez-Sánchez H, Cecilia JM, García JM. High-throughput parallel blind virtual screening using BINDSURF. BMC Bioinformatics 2012; 13(Suppl. 14): S13.
[http://dx.doi.org/10.1186/1471-2105-13-S14-S13] [PMID: 23095663]
[34]
Tian W, Chen C, Lei X, Zhao J, Liang J. CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res 2018; 46(W1): W363-7.
[http://dx.doi.org/10.1093/nar/gky473] [PMID: 29860391]
[35]
Daina A, Michielin O, Zoete V. iLOGP: A simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. J Chem Inf Model 2014; 54(12): 3284-301.
[http://dx.doi.org/10.1021/ci500467k] [PMID: 25382374]
[36]
Daina A, Zoete V. A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules. ChemMedChem 2016; 11(11): 1117-21.
[http://dx.doi.org/10.1002/cmdc.201600182] [PMID: 27218427]
[37]
Yang Y, Huang Y, Wang Z, et al. HDAC10 promotes lung cancer proliferation via AKT phosphorylation. Oncotarget 2016; 7(37): 59388-401.
[http://dx.doi.org/10.18632/oncotarget.10673] [PMID: 27449083]
[38]
Wiederstein M, Sippl MJ. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 2007; 35(Web Server issue): W407-10.
[http://dx.doi.org/10.1093/nar/gkm290] [PMID: 17517781]
[39]
Yoon H, Liu RH. Effect of 2α-hydroxyursolic acid on NF-kappaB activation induced by TNF-α in human breast cancer MCF-7 cells. J Agric Food Chem 2008; 56(18): 8412-7.
[http://dx.doi.org/10.1021/jf8012844] [PMID: 18700741]
[40]
Kim J, Ho Y, Song G, Kim D, Jeong Y, Liu K, et al. Ursolic acid and its natural derivative corosolic acid suppress the proliferation of APC-mutated colon cancer cells through promotion of β -catenin degradation. Food Chem Toxicol [Internet] Elsevier Ltd 2014; 67: 87-95.
[41]
Hao Y, Huang J, Ma Y, et al. Asiatic acid inhibits proliferation, migration and induces apoptosis by regulating Pdcd4 via the PI3K/Akt/mTOR/p70S6K signaling pathway in human colon carcinoma cells. Oncol Lett 2018; 15(6): 8223-30.
[http://dx.doi.org/10.3892/ol.2018.8417] [PMID: 29805556]
[42]
Zhang DM, Xu HG, Wang L, et al. Betulinic acid and its derivatives as potential antitumor agents. Med Res Rev 2015; 35(6): 1127-55.
[http://dx.doi.org/10.1002/med.21353] [PMID: 26032847]
[43]
Umehara K, Takagi R, Kuroyanagi M, Ueno A, Taki T, Chen YJ. Studies on differentiation-inducing activities of triterpenes. Chem Pharm Bull (Tokyo) 1992; 40(2): 401-5.
[http://dx.doi.org/10.1248/cpb.40.401] [PMID: 1606636]
[44]
Sharif T, Martell E, Dai C, et al. HDAC6 differentially regulates autophagy in stem-like versus differentiated cancer cells. Autophagy 2019; 15(4): 686-706.
[http://dx.doi.org/10.1080/15548627.2018.1548547] [PMID: 30444165]
[45]
Numata A, Yang P, Takahashi C, Fujiki R, Nabae M, Fujita E. Cytotoxic triterpenes from a Chinese medicine, Goreishi. Chem Pharm Bull (Tokyo) 1989; 37(3): 648-51.
[http://dx.doi.org/10.1248/cpb.37.648] [PMID: 2752475]
[46]
Kangsamaksin T, Chaithongyot S, Wootthichairangsan C, Hanchaina R, Tangshewinsirikul C, Svasti J. Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-α. PLoS One 2017; 12(12)e0189628
[http://dx.doi.org/10.1371/journal.pone.0189628] [PMID: 29232409]
[47]
Prasad S, Kalra N, Shukla Y. Induction of apoptosis by lupeol and mango extract in mouse prostate and LNCaP cells. Nutr Cancer 2008; 60(1): 120-30.
[http://dx.doi.org/10.1080/01635580701613772] [PMID: 18444143]
[48]
Qin XJ, Yu Q, Yan H, et al. Meroterpenoids with Antitumor Activities from Guava (Psidium guajava). J Agric Food Chem 2017; 65(24): 4993-9.
[http://dx.doi.org/10.1021/acs.jafc.7b01762] [PMID: 28578580]
[49]
Rizzo LY, Longato GB, Ruiz ALG, et al. In vitro, in vivo and in silico analysis of the anticancer and estrogen-like activity of guava leaf extracts. Curr Med Chem 2014; 21(20): 2322-30.
[http://dx.doi.org/10.2174/0929867321666140120120031] [PMID: 24438525]

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