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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Research Article

Developing a Multi-target Model to Predict the Activity of Monoamine Oxidase A and B Drugs

Author(s): Riccardo Concu*, Michael González-Durruthy* and Maria Natália D.S. Cordeiro*

Volume 20, Issue 18, 2020

Page: [1593 - 1600] Pages: 8

DOI: 10.2174/1568026620666200603121224

Price: $65

Abstract

Introduction: Monoamine oxidase inhibitors (MAOIs) are compounds largely used in the treatment of Parkinson’s disease (PD), Alzheimer’s disease and other neuropsychiatric disorders since they are closely related to the MAO enzymes activity. The two isoforms of the MAO enzymes, MAO-A and MAO-B, are responsible for the degradation of monoamine neurotransmitters and due to this, relevant efforts have been devoted to finding new compounds with more selectivity and less side effects. One of the most used approaches is based on the use of computational approaches since they are time and money-saving and may allow us to find a more relevant structure-activity relationship.

Objective: In this manuscript, we will review the most relevant computational approaches aimed at the prediction and development of new MAO inhibitors. Subsequently, we will also introduce a new multitask model aimed at predicting MAO-A and MAO-B inhibitors.

Methods: The QSAR multi-task model herein developed was based on the use of the linear discriminant analysis. This model was developed gathering 5,759 compounds from the public dataset Chembl. The molecular descriptors used was calculated using the Dragon software. Classical statistical tests were performed to check the validity and robustness of the model.

Results: The herein proposed model is able to correctly classify all the 5,759 compounds. All the statistical performed tests indicated that this model is robust and reproducible.

Conclusion: MAOIs are compounds of large interest since they are largely used in the treatment of very serious illness. These inhibitors may lose efficacy and produce severe side effects. Due to this, the development of selective MAO-A or MAO-B inhibitors is crucial for the treatment of these diseases and their effects. The herein proposed multi-target QSAR model may be a relevant tool in the development of new and more selective MAO inhibitors.

Keywords: MAO inhibitors, QSAR, Linear discriminant analysis, Multi-task model, Machine learning, Parkinson's disease.

« Previous Next »
[1]
Abell, C.W.; Kwan, S.W. Molecular characterization of monoamine oxidases A and B. Prog. Nucleic Acid Res. Mol. Biol., 2001, 65, 129-156.
[http://dx.doi.org/10.1016/S0079-6603(00)65004-3] [PMID: 11008487]
[2]
Edmondson, D.E.; Binda, C.; Wang, J.; Upadhyay, A.K.; Mattevi, A. Molecular and mechanistic properties of the membrane-bound mitochondrial monoamine oxidases. Biochemistry, 2009, 48(20), 4220-4230.
[http://dx.doi.org/10.1021/bi900413g] [PMID: 19371079]
[3]
Edmondson, D.E.; Mattevi, A.; Binda, C.; Li, M.; Hubálek, F. Structure and mechanism of monoamine oxidase. Curr. Med. Chem., 2004, 11(15), 1983-1993.
[http://dx.doi.org/10.2174/0929867043364784] [PMID: 15279562]
[4]
Shih, J.C.; Chen, K. Regulation of MAO-A and MAO-B gene expression. Curr. Med. Chem., 2004, 11(15), 1995-2005.
[http://dx.doi.org/10.2174/0929867043364757] [PMID: 15279563]
[5]
Garrick, N.A.; Murphy, D.L. Monoamine oxidase type A: differences in selectivity towards l-norepinephrine compared to serotonin. Biochem. Pharmacol., 1982, 31(24), 4061-4066.
[http://dx.doi.org/10.1016/0006-2952(82)90656-6] [PMID: 7159481]
[6]
Figueiredo, I.V.; Caramona, M.; Paiva, M.Q.; Guimarães, S. The role of MAO-A and MAO-B in the metabolic degradation of noradrenaline in human arteries. J. Auton. Pharmacol., 1998, 18(2), 123-128.
[http://dx.doi.org/10.1046/j.1365-2680.1998.1820123.x] [PMID: 9730267]
[7]
Riederer, P.; Youdim, M.B. Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. J. Neurochem., 1986, 46(5), 1359-1365.
[http://dx.doi.org/10.1111/j.1471-4159.1986.tb01747.x] [PMID: 2420928]
[8]
Finberg, J. P.; Youdim, M. B. Selective MAO A and B inhibitors: their mechanism of action and pharmacology. Neuropharmacology, 1983, 22(3 Spec No), 441-446.
[9]
Yáñez, M.; Padín, J.F.; Arranz-Tagarro, J.A.; Camiña, M.; Laguna, R. History and therapeutic use of MAO-A inhibitors: a historical perspective of mao-a inhibitors as antidepressant drug. Curr. Top. Med. Chem., 2012, 12(20), 2275-2282.
[http://dx.doi.org/10.2174/156802612805220011] [PMID: 23231399]
[10]
Bortolato, M.; Shih, J.C. Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence. Int. Rev. Neurobiol., 2011, 100, 13-42.
[http://dx.doi.org/10.1016/B978-0-12-386467-3.00002-9] [PMID: 21971001]
[11]
Youdim, M.B.; Edmondson, D.; Tipton, K.F. The therapeutic potential of monoamine oxidase inhibitors. Nat. Rev. Neurosci., 2006, 7(4), 295-309.
[http://dx.doi.org/10.1038/nrn1883] [PMID: 16552415]
[12]
Wu, Y-H.; Fischer, D.F.; Swaab, D.F. A promoter polymorphism in the monoamine oxidase A gene is associated with the pineal MAOA activity in Alzheimer’s disease patients. Brain Res., 2007, 1167, 13-19.
[http://dx.doi.org/10.1016/j.brainres.2007.06.053] [PMID: 17692293]
[13]
Hinson, V.K. Parkinson’s disease and motor fluctuations. Curr. Treat. Options Neurol., 2010, 12(3), 186-199.
[http://dx.doi.org/10.1007/s11940-010-0067-8] [PMID: 20842581]
[14]
Chavarria, D.; Fernandes, C.; Silva, V.; Silva, C.; Gil-Martins, E.; Soares, P.; Silva, T.; Silva, R.; Remião, F.; Oliveira, P.J.; Borges, F. Design of novel monoamine oxidase-B inhibitors based on piperine scaffold: Structure-activity-toxicity, drug-likeness and efflux transport studies. Eur. J. Med. Chem., 2020, 185111770
[http://dx.doi.org/10.1016/j.ejmech.2019.111770] [PMID: 31711793]
[15]
Which MAO-B inhibitor for Parkinson’s disease? Drug Ther. Bull., 2019, 57(1), 6.
[http://dx.doi.org/10.1136/dtb.2018.000051] [PMID: 30567849]
[16]
Edmondson, D.E.; Binda, C. Monoamine oxidases. Subcell. Biochem., 2018, 87, 117-139.
[http://dx.doi.org/10.1007/978-981-10-7757-9_5] [PMID: 29464559]
[17]
Schapira, A.H. Monoamine oxidase B inhibitors for the treatment of Parkinson’s disease: a review of symptomatic and potential disease-modifying effects. CNS Drugs, 2011, 25(12), 1061-1071.
[http://dx.doi.org/10.2165/11596310-000000000-00000] [PMID: 22133327]
[18]
Fahn, S.; Oakes, D.; Shoulson, I.; Kieburtz, K.; Rudolph, A.; Lang, A.; Olanow, C.W.; Tanner, C.; Marek, K. Parkinson Study Group. Levodopa and the progression of Parkinson’s disease. N. Engl. J. Med., 2004, 351(24), 2498-2508.
[http://dx.doi.org/10.1056/NEJMoa033447] [PMID: 15590952]
[19]
Rajput, A.; Rajput, A.H. Parkinson’s disease management strategies. Expert Rev. Neurother., 2006, 6(1), 91-99.
[http://dx.doi.org/10.1586/14737175.6.1.91] [PMID: 16466316]
[20]
Das, B.; Modi, G.; Dutta, A. Dopamine D3 agonists in the treatment of Parkinson’s disease. Curr. Top. Med. Chem., 2015, 15(10), 908-926.
[http://dx.doi.org/10.2174/156802661510150328223428] [PMID: 25832718]
[21]
Matute, M.S.; Matute, R.; Merino, P. Design and synthesis of dopaminergic agonists. Curr. Med. Chem., 2016, 23(25), 2790-2825.
[http://dx.doi.org/10.2174/0929867323666160504103621] [PMID: 27142290]
[22]
Montastruc, J.L.; Rascol, O.; Senard, J.M. Current status of dopamine agonists in Parkinson’s disease management. Drugs, 1993, 46(3), 384-393.
[http://dx.doi.org/10.2165/00003495-199346030-00005] [PMID: 7693430]
[23]
De Deurwaerdère, P. Cariprazine:New dopamine biased agonist for neuropsychiatric disorders. Drugs Today (Barc), 2016, 52(2), 97-110.
[http://dx.doi.org/10.1358/dot.2016.52.2.2461868] [PMID: 27092339]
[24]
Hagell, P.; Odin, P. Apomorphine in the treatment of Parkinson’s disease. J. Neurosci. Nurs., 2001, 33(1), 21-34, 37-38.
[http://dx.doi.org/10.1097/01376517-200102000-00004] [PMID: 11233359]
[25]
Stowe, R.; Ives, N.; Clarke, C.E.; Handley, K.; Furmston, A.; Deane, K.; van Hilten, J.J.; Wheatley, K.; Gray, R. Meta-analysis of the comparative efficacy and safety of adjuvant treatment to levodopa in later Parkinson’s disease. Mov. Disord., 2011, 26(4), 587-598.
[http://dx.doi.org/10.1002/mds.23517] [PMID: 21370258]
[26]
Kovacs, N.; Nagy, F.; Balas, I.; Komoly, S.; Janszky, J. Oxcarbazepine may induce psychotic symptoms in Parkinson’s disease. Epilepsy Behav., 2008, 12(3), 492-493.
[http://dx.doi.org/10.1016/j.yebeh.2007.12.010] [PMID: 18222110]
[27]
Singer, C. Adverse effects in the treatment of Parkinson’s disease. Expert Rev. Neurother., 2002, 2(1), 105-118.
[http://dx.doi.org/10.1586/14737175.2.1.105] [PMID: 19811020]
[28]
Sturza, A.; Popoiu, C.M.; Ionică, M.; Duicu, O.M.; Olariu, S.; Muntean, D.M.; Boia, E.S. Monoamine oxidase-related vascular oxidative stress in diseases associated with inflammatory burden. Oxid. Med. Cell. Longev., 2019, 2019, 1-8.
[http://dx.doi.org/10.1155/2019/8954201] [PMID: 31178977]
[29]
Maggiorani, D.; Manzella, N.; Edmondson, D.E.; Mattevi, A.; Parini, A.; Binda, C.; Mialet-Perez, J. Monoamine oxidases, oxidative stress, and altered mitochondrial dynamics in cardiac ageing. Oxid. Med. Cell. Longev., 2017, 2017, 1-8.
[http://dx.doi.org/10.1155/2017/3017947] [PMID: 28546851]
[30]
Cui, Y.; Liu, K.W.; Liang, Y.; Ip, M.S.; Mak, J.C. Inhibition of monoamine oxidase-B by selegiline reduces cigarette smoke-induced oxidative stress and inflammation in airway epithelial cells. Toxicol. Lett., 2017, 268, 44-50.
[http://dx.doi.org/10.1016/j.toxlet.2017.01.005] [PMID: 28108387]
[31]
Sturza, A.; Duicu, O.M.; Vaduva, A.; Dănilă, M.D.; Noveanu, L.; Varró, A.; Muntean, D.M. Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes. Can. J. Physiol. Pharmacol., 2015, 93(7), 555-561.
[http://dx.doi.org/10.1139/cjpp-2014-0544] [PMID: 25996256]
[32]
Prado-Prado, F.; García-Mera, X.; Escobar, M.; Sobarzo-Sánchez, E.; Yañez, M.; Riera-Fernandez, P.; González-Díaz, H. 2D MI-DRAGON: a new predictor for protein-ligands interactions and theoretic-experimental studies of US FDA drug-target network, oxoisoaporphine inhibitors for MAO-A and human parasite proteins. Eur. J. Med. Chem., 2011, 46(12), 5838-5851.
[http://dx.doi.org/10.1016/j.ejmech.2011.09.045] [PMID: 22005185]
[33]
Santana, L.; Uriarte, E.; González-Díaz, H.; Zagotto, G.; Soto-Otero, R.; Méndez-Alvarez, E. A QSAR model for in silico screening of MAO-A inhibitors. Prediction, synthesis, and biological assay of novel coumarins. J. Med. Chem., 2006, 49(3), 1149-1156.
[http://dx.doi.org/10.1021/jm0509849] [PMID: 16451079]
[34]
Shelke, S.M.; Bhosale, S.H.; Dash, R.C.; Suryawanshi, M.R.; Mahadik, K.R. Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening. Bioorg. Med. Chem. Lett., 2011, 21(8), 2419-2424.
[http://dx.doi.org/10.1016/j.bmcl.2011.02.072] [PMID: 21397504]
[35]
Mathew, B.; Adeniyi, A.A.; Dev, S.; Joy, M.; Ucar, G.; Mathew, G.E.; Singh-Pillay, A.; Soliman, M.E. Pharmacophore-based 3D-QSAR analysis of thienyl chalcones as a new class of human MAO-B inhibitors: investigation of combined quantum chemical and molecular dynamics approach. J. Phys. Chem. B, 2017, 121(6), 1186-1203.
[http://dx.doi.org/10.1021/acs.jpcb.6b09451] [PMID: 28084742]
[36]
Pisani, L.; Farina, R.; Nicolotti, O.; Gadaleta, D.; Soto-Otero, R.; Catto, M.; Di Braccio, M.; Mendez-Alvarez, E.; Carotti, A. In silico design of novel 2H-chromen-2-one derivatives as potent and selective MAO-B inhibitors. Eur. J. Med. Chem., 2015, 89, 98-105.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.029] [PMID: 25462230]
[37]
Gritsch, S.; Guccione, S.; Hoffmann, R.; Cambria, A.; Raciti, G.; Langer, T. A 3D QSAR study of monoamino oxidase-B inhibitors using the chemical function based pharmacophore generation approach. J. Enzyme Inhib., 2001, 16(3), 199-215.
[http://dx.doi.org/10.1080/14756360109162369] [PMID: 11697041]
[38]
Speck-Planche, A.; Kleandrova, V.V. QSAR and molecular docking techniques for the discovery of potent monoamine oxidase B inhibitors: computer-aided generation of new rasagiline bioisosteres. Curr. Top. Med. Chem., 2012, 12(16), 1734-1747.
[http://dx.doi.org/10.2174/1568026611209061734] [PMID: 23030609]
[39]
Chimenti, F.; Maccioni, E.; Secci, D.; Bolasco, A.; Chimenti, P.; Granese, A.; Befani, O.; Turini, P.; Alcaro, S.; Ortuso, F.; Cirilli, R.; La Torre, F.; Cardia, M.C.; Distinto, S. Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)- pyrazole derivatives. J. Med. Chem., 2005, 48(23), 7113-7122.
[http://dx.doi.org/10.1021/jm040903t] [PMID: 16279769]
[40]
Carotti, A.; Catto, M.; Leonetti, F.; Campagna, F.; Soto-Otero, R.; Méndez-Alvarez, E.; Thull, U.; Testa, B.; Altomare, C. Synthesis and monoamine oxidase inhibitory activity of new pyridazine-, pyrimidine- and 1,2,4-triazine-containing tricyclic derivatives. J. Med. Chem., 2007, 50(22), 5364-5371.
[http://dx.doi.org/10.1021/jm070728r] [PMID: 17910428]
[41]
Helguera, A.M.; Pérez-Garrido, A.; Gaspar, A.; Reis, J.; Cagide, F.; Vina, D.; Cordeiro, M.N.D.S.; Borges, F. Combining QSAR classification models for predictive modeling of human monoamine oxidase inhibitors. Eur. J. Med. Chem., 2013, 59, 75-90.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.035] [PMID: 23207409]
[42]
Santana, L.; González-Díaz, H.; Quezada, E.; Uriarte, E.; Yáñez, M.; Viña, D.; Orallo, F. Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors. J. Med. Chem., 2008, 51(21), 6740-6751.
[http://dx.doi.org/10.1021/jm800656v] [PMID: 18834112]
[43]
Molina, E.; Sobarzo-Sanchez, E.; Speck-Planche, A.; Matos, M.J.; Uriarte, E.; Santana, L.; Yanez, M.; Orallo, F. Monoamino oxidase A: an interesting pharmacological target for the development of multi-target QSAR. Mini Rev. Med. Chem., 2012, 12(10), 947-958.
[http://dx.doi.org/10.2174/138955712802762383] [PMID: 22420572]
[44]
Gaulton, A.; Hersey, A.; Nowotka, M.; Bento, A.P.; Chambers, J.; Mendez, D.; Mutowo, P.; Atkinson, F.; Bellis, L.J.; Cibrián-Uhalte, E.; Davies, M.; Dedman, N.; Karlsson, A.; Magariños, M.P.; Overington, J.P.; Papadatos, G.; Smit, I.; Leach, A.R. The ChEMBL database in 2017. Nucleic Acids Res., 2017, 45(D1), D945-D954.
[http://dx.doi.org/10.1093/nar/gkw1074] [PMID: 27899562]
[45]
Kode, S. Dragon (software for molecular descriptor calculation),7.0.10., 2017.
[46]
TIBCO Software Inc Statistica (data analysis software system), 13,, 2018.
[47]
Wang, H.; Yan, L.; Huang, H.; Ding, C. From protein sequence to protein function via multi-label linear discriminant analysis. IEEE/ACM Trans Comput Biol Bioinform, 2017, 14(3), 503-513.
[http://dx.doi.org/10.1109/TCBB.2016.2591529]
[48]
Matthews, B.W. Comparison of the predicted and observed secondary structure of T4 phage lysozyme. Biochim. Biophys. Acta, 1975, 405(2), 442-451.
[http://dx.doi.org/10.1016/0005-2795(75)90109-9] [PMID: 1180967]

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