zbMATH — the first resource for mathematics

Reverse screening on indicaxanthin from Opuntia ficus-indica as natural chemoactive and chemopreventive agent. (English) Zbl 1406.92219
Summary: Indicaxanthin is a bioactive and bioavailable betalain pigment extracted from Opuntia ficus-indica fruits. Indicaxanthin has pharmacokinetic proprieties, rarely found in other phytochemicals, and it has been demonstrated that it provides a broad-spectrum of pharmaceutical activity, exerting anti-proliferative, anti-inflammatory, and neuromodulator effects. The discovery of the Indicaxanthin physiological targets plays an important role in understanding the biochemical mechanism. In this study, combined reverse pharmacophore mapping, reverse docking, and text-based database search identified inositol trisphosphate 3-kinase (ITP3K-A), glutamate carboxypeptidase II (GCPII), leukotriene-A4 hydrolase (LTA4H), phosphoserine phosphatase (HPSP), phosphodiesterase 4D (PDE4D), AMPA receptor (GluA3 and GluA2 subunits) and Kainate receptor (GluK1 isoform) as potential targets for indicaxanthin. These targets are implicated in neuromodulation, and inflammatory regulation, normally expressed mostly in the CNS, and expressed (or overexpressed) in cancer tissues (i.e. breast, thyroid, and prostate cancer cells). Moreover, this study provides qualitative and quantitative information about dynamic interactions of indicaxanthin at the binding site of target proteins, through molecular dynamics simulations and MM-GBSA.
92C40 Biochemistry, molecular biology
92C50 Medical applications (general)
Full Text: DOI
[1] Adasme-Carreño, F.; Muñoz-Gutierrez, C.; Caballero, J.; Alzate-Morales, J. H., Performance of the MM/GBSA scoring using a binding site hydrogen bond network-based frame selection: the protein kinase case, Phys. Chem. Chem. Phys., 16, 14047-14058, (2014)
[2] Allegra, M.; Carletti, F.; Gambino, G.; Tutone, M.; Attanzio, A.; Tesoriere, L.; Ferraro, G.; Sardo, P.; Almerico, A. M.; Livrea, M. A., Indicaxanthin from opuntia ficus-indica crosses the blood-brain barrier and modulates neuronal bioelectric activity in rat hippocampus at dietary-consistent amounts, J. Agric. Food Chem., 63, 7353-7360, (2015)
[3] Allegra, M.; D’Acquisto, F.; Tesoriere, L.; Attanzio, A.; Livrea, M. A., Pro-oxidant activity of indicaxanthin from opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages, Redox Biol., 2, 892-900, (2014)
[4] Allegra, M.; Ianaro, A.; Tersigni, M.; Panza, E.; Tesoriere, L.; Livrea, M. A., Indicaxanthin from cactus pear fruit exerts anti-inflammatory effects in carrageenin-induced rat pleurisy, J. Nutr., 144, 185-192, (2014)
[5] Allen, M., Introduction to molecular dynamics simulation, Comput. Soft Matter From Synth. Polym., 23, 1-28, (2004)
[6] Almerico, A. M.; Tutone, M.; Guarcello, A.; Lauria, A., In vitro and in silico studies of polycondensed diazine systems as anti-parasitic agents, Bioorganic Med. Chem. Lett., (2012)
[7] Anighoro, A.; Bajorath, J.; Rastelli, G., Polypharmacology: challenges and opportunities in drug discovery, J. Med. Chem., 57, 7874-7887, (2014)
[8] Baldassano, S.; Rotondo, A.; Serio, R.; Livrea, M. A.; Tesoriere, L.; Mulè, F., Inhibitory effects of indicaxanthin on mouse ileal contractility: analysis of the mechanism of action, Eur. J. Pharmacol., 658, 200-205, (2011)
[9] Bas, D. C.; Rogers, D. M.; Jensen, J. H., Very fast prediction and rationalization of pka values for protein-ligand complexes, Proteins Struct. Funct. Genet., 73, 765-783, (2008)
[10] Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E., The protein data bank, Nucleic Acids Res., 28, 235-242, (2000)
[11] Bowers, K.; Chow, E.; Xu, H.; Dror, R.; Eastwood, M.; Gregersen, B.; Klepeis, J.; Kolossvary, I.; Moraes, M.; Sacerdoti, F.; Salmon, J.; Shan, Y.; Shaw, D., Scalable algorithms for molecular dynamics simulations on commodity clusters, ACM/IEEE SC 2006 Conference (SC’06), pp., 43-43, (2006)
[12] Butera, D.; Tesoriere, L.; Di Gaudio, F.; Bongiorno, A.; Allegra, M.; Pintaudi, A. M.; Kohen, R.; Livrea, M. A., Antioxidant activities of Sicilian prickly pear (opuntia ficus indica) fruit extracts and reducing properties of its betalains: betanin and indicaxanthin, J. Agric. Food Chem, 50, 6895-6901, (2002)
[13] Chemi, G.; Gemma, S.; Campiani, G.; Brogi, S.; Butini, S.; Brindisi, M., Computational tool for fast in silico evaluation of herg K+ channel affinity, Front. Chem., 5, (2017)
[14] Chen, X.; Lin, Y.; Gilson, M. K., The binding database: overview and User’s guide, Biopolymers, (2001)
[15] Chen, X.; Lin, Y.; Liu, M.; Gilson, M. K., The binding database: data management and interface design, Bioinformatics, 18, 130-139, (2002)
[16] Chen, X.; Liu, M.; Gilson, M. K., Bindingdb: a web-accessible molecular recognition database, Comb. Chem. High Throughput Screen, 4, 719-725, (2001)
[17] Chen, X.; Wang, S.; Wu, N.; Yang, C., Leukotriene A4 hydrolase as a target for cancer prevention and therapy, Curr. Cancer Drug Targets, 4, 267-283, (2004)
[18] Chen, Y. Z.; Zhi, D. G., Ligand - protein inverse docking and its potential use in the computer search of protein targets of a small molecule, Proteins Struct. Funct. Genet., 43, 217-226, (2001)
[19] Cho, A. E.; Guallar, V.; Berne, B. J.; Friesner, R., Importance of accurate charges in molecular docking: quantum mechanical/molecular mechanical (QM/MM) approach, J. Comput. Chem., 26, 915-931, (2005)
[20] Conner, D. A., Mouse embryo fibroblast (MEF) feeder cell preparation, Current Protocols in Molecular Biology, (2001)
[21] Dias, G. P.; Cavegn, N.; Nix, A.; do Nascimento Bevilaqua, M. C.; Stangl, D.; Zainuddin, M. S.; Nardi, aE.; Gardino, P. F.; Thuret, S., The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioural effects on depression and anxiety, Oxid. Med. Cell Longev, 2012, (2012)
[22] Drews, J., Strategic choices facing the pharmaceutical industry: a case for innovation, Drug Discov. Today, (1997)
[23] Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S., Glide: a new approach for rapid, accurate docking and scoring. 1. method and assessment of docking accuracy, J. Med. Chem, 47, 1739-1749, (2004)
[24] Friesner, R. A.; Guallar, V., Ab initio quantum chemical and mixed quantum mechanics/molecular mechanics (qm/mm) methods for studying enzymatic catalysis, Annu. Rev. Phys. Chem., 56, 389-427, (2005)
[25] Friesner, R. A.; Murphy, R. B.; Repasky, M. P.; Frye, L. L.; Greenwood, J. R.; Halgren, T. A.; Sanschagrin, P. C.; Mainz, D. T., Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes, J. Med. Chem., 49, 6177-6196, (2006)
[26] Gilson, M. K.; Liu, T.; Baitaluk, M.; Nicola, G.; Hwang, L.; Chong, J., Bindingdb in 2015: a public database for medicinal chemistry, computational chemistry and systems pharmacology, Nucleic Acids Res., 44, D1045-D1053, (2016)
[27] Halgren, T. A.; Murphy, R. B.; Friesner, R. A.; Beard, H. S.; Frye, L. L.; Pollard, W. T.; Banks, J. L., Glide: a new approach for rapid, accurate docking and scoring. 2. enrichment factors in database screening, J. Med. Chem, 47, 1750-1759, (2004)
[28] Homeyer, N.; Gohlke, H., Free energy calculations by the molecular mechanics Poisson-Boltzmann surface area method, Mol. Inform., 31, 114-122, (2012)
[29] Hou, T.; Yu, R., Molecular dynamics and free energy studies on the wild-type and double mutant HIV-1 protease complexed with amprenavir and two amprenavir-related inhibitors: mechanism for binding and drug resistance, J. Med. Chem., 50, 1177-1188, (2007)
[30] Huang, N.; Shoichet, B. K.; Irwin, J. J., Benchmarking sets for molecular docking, J. Med. Chem., 49, 6789-6801, (2006)
[31] Hughes, J. P.; Rees, S.; Kalindjian, S. B.; Philpott, K. L., Principles of early drug discovery, Br. J. Pharmacol., 162, 1239-1249, (2011)
[32] Hurle, M. R.; Yang, L.; Xie, Q.; Rajpal, D. K.; Sanseau, P.; Agarwal, P., Computational drug repositioning: from data to therapeutics, Clin. Pharmacol. Ther., (2013)
[33] Irwin, J. J.; Shoichet, B. K., ZINC - a free database of commercially available compounds for virtual screening, J. Chem. Inf. Model., 45, 177-182, (2005)
[34] Jacobson, M. P.; Pincus, D. L.; Rapp, C. S.; Day, T. J.; Honig, B.; Shaw, D. E.; Friesner, R. A.; Zhang, C.; Liu, S.; Zhou, Y.; Rohl, C. A.; Strauss, C. E.; Chivian, D.; Baker, D., A hierarchical approach to all-atom protein loop prediction\raccurate and efficient loop selections by the DFIRE-based all-atom statistical potential\rmodeling structurally variable regions in homologous proteins with rosetta, Proteins, 55, 351-367, (2004)
[35] Karplus, M.; McCammon, J. A., Molecular dynamics simulations of biomolecules, Nat. Struct. Biol., 9, 646-652, (2002)
[36] Kharkar, P. S.; Warrier, S.; Gaud, R. S., Reverse docking: a powerful tool for drug repositioning and drug rescue, Future Med. Chem., 6, 333-342, (2014)
[37] Kim, H. Y.; Heo, Y. S.; Kim, J. H.; Park, M. H.; Moon, J.; Kim, E.; Kwon, D.; Yoon, J.; Shin, D.; Jeong, E. june; Yong Park, S.; Lee, T. G.; Jeon, Y. H.; Ro, S.; Cho, J. M.; Hwang, K. Y., Molecular basis for the local conformational rearrangement of human phosphoserine phosphatase, J. Biol. Chem., 277, 46651-46658, (2002)
[38] Kortagere, S.; Ekins, S., Troubleshooting computational methods in drug discovery, J. Pharmacol. Toxicol. Methods, 61, 67-75, (2014)
[39] Lauria, A.; Tutone, M.; Almerico, A. M., Virtual lock-and-key approach: the in silico revival of fischer model by means of molecular descriptors, Eur. J. Med. Chem., (2011)
[40] Lauria, A.; Tutone, M.; Barone, G.; Almerico, A. M., Multivariate analysis in the identification of biological targets for designed molecular structures: the BIOTA protocol, Eur. J. Med. Chem., (2014)
[41] Liu, T.; Lin, Y.; Wen, X.; Jorissen, R. N.; Gilson, M. K., Bindingdb: a web-accessible database of experimentally determined protein-ligand binding affinities, Nucleic Acids Res., 35, (2007)
[42] Liu, X.; Ouyang, S.; Yu, B.; Liu, Y.; Huang, K.; Gong, J.; Zheng, S.; Li, Z.; Li, H.; Jiang, H., Pharmmapper server: a web server for potential drug target identification using pharmacophore mapping approach, Nucleic Acids Res., 38, W609-W614, (2010)
[43] Luo, Q.; Zhao, L.; Hu, J.; Jin, H.; Liu, Z.; Zhang, L., The scoring bias in reverse docking and the score normalization strategy to improve success rate of target fishing, PLoS One, 12, (2017)
[44] Madhavi Sastry, G.; Adzhigirey, M.; Day, T.; Annabhimoju, R.; Sherman, W., Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments, J. Comput. Aided Mol. Des., 27, 221-234, (2013)
[45] Massova, I.; Kollman, P. A., Combined molecularmechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding, Perspect. Drug Discov. Des., 18, 113-135, (2000)
[46] Mesters, J. R.; Henning, K.; Hilgenfeld, R., Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA, Acta Crystallogr. Sect. D Biol. Crystallogr., 63, 508-513, (2007)
[47] Murphy, R. B.; Philipp, D. M.; Friesner, R. A., A mixed quantum mechanics/molecular mechanics (QM/MM) method for large-scale modeling of chemistry in protein environments, J. Comput. Chem., 21, 1442-1457, (2000)
[48] Nabuurs, S. B.; Wagener, M.; De Vlieg, J., A flexible approach to induced fit docking, J. Med. Chem., 50, 6507-6518, (2007)
[49] Naselli, F.; Belshaw, N. J.; Gentile, C.; Tutone, M.; Tesoriere, L.; Livrea, M. A.; Caradonna, F., Phytochemical indicaxanthin inhibits colon cancer cell growth and affects the DNA methylation status by influencing epigenetically modifying enzyme expression and activity, J. Nutrigenet. Nutrigenom., 8, 114-127, (2015)
[50] Naselli, F.; Tesoriere, L.; Caradonna, F.; Bellavia, D.; Attanzio, A.; Gentile, C.; Livrea, M. A., Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from opuntia ficus-indica associated with re-activation of the onco-suppressor p16INK4a gene in human colorectal carcinoma (caco-2) cells, Biochem. Biophys. Res. Commun., 450, 652-658, (2014)
[51] Paolino, M.; Brindisi, M.; Vallone, A.; Butini, S.; Campiani, G.; Nannicini, C.; Giuliani, G.; Anzini, M.; Lamponi, S.; Giorgi, G.; Sbardella, D.; Ferraris, D. M.; Marini, S.; Coletta, M.; Palucci, I.; Minerva, M.; Delogu, G.; Pepponi, I.; Goletti, D.; Cappelli, A.; Gemma, S.; Brogi, S., Development of potent inhibitors of the mycobacterium tuberculosis virulence factor zmp1 and evaluation of their effect on mycobacterial survival inside macrophages, Chem. Med. Chem., 13, 422-430, (2018)
[52] Reddy, A. S.; Tan, Z.; Zhang, S., Curation and analysis of multitargeting agents for polypharmacological modeling, J. Chem. Inf. Model., 54, 2536-2543, (2014)
[53] Rendeiro, C.; Guerreiro, J. D.T.; Williams, C. M.; Spencer, J. P.E., Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects, Proc. Nutr. Soc., 71, 246-262, (2012)
[54] Rognan, D., Computational approaches to target fishing and ligand profiling, (AIP Conference Proceedings, (2012)), 157-164
[55] Salam, N. K.; Huang, T. H.W.; Kota, B. P.; Kim, M. S.; Li, Y.; Hibbs, D. E., Novel PPAR-gamma agonists identified from a natural product library: a virtual screening, induced-fit docking and biological assay study, Chem. Biol. Drug Des., 71, 57-70, (2008)
[56] Schomburg, K. T.; Rarey, M., What is the potential of structure-based target prediction methods, Future Med. Chem, 6, 1987-1989, (2014)
[57] Shamsara, J., Evaluation of 11 scoring functions performance on matrix metalloproteinases, Int. J. Med. Chem., 2014, (2014)
[58] Shelley, J. C.; Cholleti, A.; Frye, L. L.; Greenwood, J. R.; Timlin, M. R.; Uchimaya, M., Epik: A software program for pka prediction and protonation state generation for drug-like molecules, J. Comput. Aided Mol. Des., 21, 681-691, (2007)
[59] Sherman, W.; Beard, H. S.; Farid, R., Use of an induced fit receptor structure in virtual screening, Chem. Biol. Drug Des., (2006)
[60] Sherman, W.; Day, T.; Jacobson, M. P.; Friesner, R. A.; Farid, R., Novel procedure for modeling ligand/receptor induced fit effects, J. Med. Chem., 49, 534-553, (2006)
[61] Spencer, J. P.E., The impact of flavonoids on memory: physiological and molecular considerations, Chem. Soc. Rev., 38, 1152, (2009)
[62] Tesoriere, L.; Attanzio, A.; Allegra, M.; Livrea, M. A., Dietary indicaxanthin from cactus pear (opuntia ficus-indica L. mill) fruit prevents eryptosis induced by oxysterols in a hypercholesterolaemia-relevant proportion and adhesion of human erythrocytes to endothelial cell layers, Br. J. Nutr., 114, 368-375, (2015)
[63] Tesoriere, L.; Gentile, C.; Angileri, F.; Attanzio, A.; Tutone, M.; Allegra, M.; Livrea, M. A., Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across caco-2 cell monolayers and influence of food matrix, Eur. J. Nutr., (2013)
[64] Thul, P. J.; Åkesson, L.; Wiking, M.; Mahdessian, D.; Geladaki, A.; Ait Blal, H.; Alm, T.; Asplund, A.; Björk, L.; Breckels, L. M.; Bäckström, A.; Danielsson, F.; Fagerberg, L.; Fall, J.; Gatto, L.; Gnann, C.; Hober, S.; Hjelmare, M.; Johansson, F.; Lee, S.; Lindskog, C.; Mulder, J.; Mulvey, C. M.; Nilsson, P.; Oksvold, P.; Rockberg, J.; Schutten, R.; Schwenk, J. M.; Sivertsson, Å.; Sjöstedt, E.; Skogs, M.; Stadler, C.; Sullivan, D. P.; Tegel, H.; Winsnes, C.; Zhang, C.; Zwahlen, M.; Mardinoglu, A.; Pontén, F.; von Feilitzen, K.; Lilley, K. S.; Uhlén, M.; Lundberg, E., A subcellular map of the human proteome, Science, 80, 356, eaal3321, (2017)
[65] Tripathi, S. K.; Singh, S. K., Insights into the structural basis of 3,5-diaminoindazoles as CDK2 inhibitors: prediction of binding modes and potency by QM-MM interaction, MESP and MD simulation, Mol. Biosyst., 10, 2189-2201, (2014)
[66] Truchon, J. F.; Bayly, C. I., Evaluating virtual screening methods: good and bad metrics for the “early recognition” problem, J. Chem. Inf. Model., 47, 488-508, (2007)
[67] Tutone, M.; Chinnici, A.; Almerico, A. M.; Perricone, U.; Sutera, F. M.; De Caro, V., Design, synthesis and preliminary evaluation of dopamine-amino acid conjugates as potential D1 dopaminergic modulators, Eur. J. Med. Chem., 124, (2016)
[68] Tutone, M.; Lauria, A.; Almerico, A. M., Theoretical determination of the pk <inf>a</inf>values of betalamic acid related to the free radical scavenger capacity: comparison between empirical and quantum chemical methods, Interdiscip. Sci. Comput. Life Sci., 8, (2016)
[69] Tutone, M.; Perricone, U.; Almerico, A. M., Conf-VLKA: a structure-based revisitation of the virtual lock-and-key approach, J. Mol. Graph. Model., 71, (2017)
[70] Uhlen, M.; Fagerberg, L.; Hallstrom, B. M.; Lindskog, C.; Oksvold, P.; Mardinoglu, A.; Sivertsson, A.; Kampf, C.; Sjostedt, E.; Asplund, A.; Olsson, I.; Edlund, K.; Lundberg, E.; Navani, S.; Szigyarto, C. A.-K.; Odeberg, J.; Djureinovic, D.; Takanen, J. O.; Hober, S.; Alm, T.; Edqvist, P.-H.; Berling, H.; Tegel, H.; Mulder, J.; Rockberg, J.; Nilsson, P.; Schwenk, J. M.; Hamsten, M.; von Feilitzen, K.; Forsberg, M.; Persson, L.; Johansson, F.; Zwahlen, M.; von Heijne, G.; Nielsen, J.; Ponten, F., Tissue-based map of the human proteome, Science, 80, 347, (2015), 1260419-1260419. doi:10.1126/science.1260419
[71] Vallone, A.; D’Alessandro, S.; Brogi, S.; Brindisi, M.; Chemi, G.; Alfano, G.; Lamponi, S.; Lee, S. G.; Jez, J. M.; Koolen, K. J.M.; Dechering, K. J.; Saponara, S.; Fusi, F.; Gorelli, B.; Taramelli, D.; Parapini, S.; Caldelari, R.; Campiani, G.; Gemma, S.; Butini, S., Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the malaria box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues, Eur. J. Med. Chem., 150, 698-718, (2018)
[72] van Gunsteren, W. F.; Berendsen, H. J.C., Computer simulation of molecular dynamics: methodology, applications, and perspectives in chemistry, Angew. Chemie Int. Ed. Engl., 29, 992-1023, (1990)
[73] Wang, H.; Khor, T. O.; Shu, L.; Su, Z.-Y.; Fuentes, F.; Lee, J.-H.; Kong, A.-N. T., Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability, Anticancer. Agents Med. Chem., 12, 1281-1305, (2012)
[74] Wang, J.; Gao, L.; Lee, Y. M.; Kalesh, K. A.; Ong, Y. S.; Lim, J.; Jee, J.-E.; Sun, H.; Lee, S. S.; Hua, Z.-C.; Lin, Q., Target identification of natural and traditional medicines with quantitative chemical proteomics approaches, Pharmacol. Ther., 162, (2016)
[75] Wang, W.; Kollman, P. A., Computational study of protein specificity: the molecular basis of HIV-1 protease drug resistance, Proc. Natl. Acad. Sci. USA, 98, 14937-14942, (2001)
[76] Wolber, G.; Seidel, T.; Bendix, F.; Langer, T., Molecule-pharmacophore superpositioning and pattern matching in computational drug design, Drug Discov. Today, 13, 23-29, (2008)
[77] Ziegler, S.; Pries, V.; Hedberg, C.; Waldmann, H., Target identification for small bioactive molecules: finding the needle in the haystack, Angew. Chemie Int. Ed., (2013)
This reference list is based on information provided by the publisher or from digital mathematics libraries. Its items are heuristically matched to zbMATH identifiers and may contain data conversion errors. It attempts to reflect the references listed in the original paper as accurately as possible without claiming the completeness or perfect precision of the matching.