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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Review Article

Positive Predictive Value Surfaces as a Complementary Tool to Assess the Performance of Virtual Screening Methods

Author(s): Juan F. Morales, Sara Chuguransky, Lucas N. Alberca, Juan I. Alice, Sofía Goicoechea, María E. Ruiz, Carolina L. Bellera and Alan Talevi*

Volume 20, Issue 14, 2020

Page: [1447 - 1460] Pages: 14

DOI: 10.2174/1871525718666200219130229

Price: $65

Abstract

Background: Since their introduction in the virtual screening field, Receiver Operating Characteristic (ROC) curve-derived metrics have been widely used for benchmarking of computational methods and algorithms intended for virtual screening applications. Whereas in classification problems, the ratio between sensitivity and specificity for a given score value is very informative, a practical concern in virtual screening campaigns is to predict the actual probability that a predicted hit will prove truly active when submitted to experimental testing (in other words, the Positive Predictive Value - PPV). Estimation of such probability is however, obstructed due to its dependency on the yield of actives of the screened library, which cannot be known a priori.

Objective: To explore the use of PPV surfaces derived from simulated ranking experiments (retrospective virtual screening) as a complementary tool to ROC curves, for both benchmarking and optimization of score cutoff values.

Methods: The utility of the proposed approach is assessed in retrospective virtual screening experiments with four datasets used to infer QSAR classifiers: inhibitors of Trypanosoma cruzi trypanothione synthetase; inhibitors of Trypanosoma brucei N-myristoyltransferase; inhibitors of GABA transaminase and anticonvulsant activity in the 6 Hz seizure model.

Results: Besides illustrating the utility of PPV surfaces to compare the performance of machine learning models for virtual screening applications and to select an adequate score threshold, our results also suggest that ensemble learning provides models with better predictivity and more robust behavior.

Conclusion: PPV surfaces are valuable tools to assess virtual screening tools and choose score thresholds to be applied in prospective in silico screens. Ensemble learning approaches seem to consistently lead to improved predictivity and robustness.

Keywords: Benchmarking, positive predictive value, ensemble learning, retrospective screen, virtual screening, enrichment.

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[1]
Triballeau, N.; Acher, F.; Brabet, I.; Pin, J.P.; Bertrand, H.O. Virtual screening workflow development guided by the “receiver operating characteristic” curve approach. Application to high throughput docking on metabotropic glutamate receptor subtype 4. J. Med. Chem., 2005, 48(7), 2534-2547.
[http://dx.doi.org/10.1021/jm049092j] [PMID: 15801843]
[2]
Yang, Y.; Zou, F.; Zhao, L.; Cheng, X.; Zha, X.; Zhang, H.; Zhou, J. Combined pharmacophore models as virtual screening protocol against brd4(1) inhibitor. Med. Chem. Res., 2016, 25, 585-595.
[http://dx.doi.org/10.1007/s00044-016-1513-2]
[3]
Swift, R.V.; Jusoh, S.A.; Offutt, T.L.; Li, E.S.; Amaro, R.E. Knowledge-Based methods to train and optimize virtual screening ensembles. J. Chem. Inf. Model., 2016, 56(5), 830-842.
[http://dx.doi.org/10.1021/acs.jcim.5b00684] [PMID: 27097522]
[4]
Wang, M.Y.; Li, P.; Qiao, P.L. the virtual screening of the drug protein with a few crystal structures based on the adaboost-SVM. Comput. Math. Methods Med., 2016., 20164809831.
[http://dx.doi.org/10.1155/2016/4809831] [PMID: 27127534]
[5]
Gani, O.A.B.S.M.; Narayanan, D.; Engh, R.A. Evaluating the predictivity of virtual screening for ABL kinase inhibitors to hinder drug resistance. Chem. Biol. Drug Des., 2013, 82(5), 506-519.
[http://dx.doi.org/10.1111/cbdd.12170] [PMID: 23746052]
[6]
Hsin, K.Y.; Matsuoka, Y.; Asai, Y.; Kamiyoshi, K.; Watanabe, T.; Kawaoka, Y.; Kitano, H. systemsDock: A web server for network pharmacology-based prediction and analysis. Nucleic Acids Res., 2016, 44(W1), W507-513.
[http://dx.doi.org/10.1093/nar/gkw335] [PMID: 27131384]
[7]
Cross, J.B.; Thompson, D.C.; Rai, B.K.; Baber, J.C.; Fan, K.Y.; Hu, Y.; Humblet, C. Comparison of several molecular docking programs: Pose prediction and virtual screening accuracy. J. Chem. Inf. Model., 2009, 49(6), 1455-1474.
[http://dx.doi.org/10.1021/ci900056c] [PMID: 19476350]
[8]
Wang, Q.; Birod, K.; Angioni, C.; Grösch, S.; Geppert, T.; Schneider, P.; Rupp, M.; Schneider, G. Spherical harmonics coefficients for ligand-based virtual screening of cyclooxygenase inhibitors. PLoS One, 2011, 6(7), e21554.
[http://dx.doi.org/10.1371/journal.pone.0021554] [PMID: 21818259]
[9]
Gantner, M.E.; Di Ianni, M.E.; Ruiz, M.E.; Talevi, A.; Bruno-Blanch, L.E. Development of conformation independent computational models for the early recognition of breast cancer resistance protein substrates. BioMed Res. Int., 2013., 2013863592.
[http://dx.doi.org/10.1155/2013/863592] [PMID: 23984415]
[10]
Alberca, L.N.; Sbaraglini, M.L.; Morales, J.F.; Dietrich, R.; Ruiz, M.D.; Pino Martínez, A.M.; Miranda, C.G.; Fraccaroli, L.; Alba Soto, C.D.; Carrillo, C.; Palestro, P.H.; Talevi, A. Cascade ligand and structure-based virtual screening to identify new trypanocidal compounds inhibiting putrescine uptake. Front. Cell. Infect. Microbiol., 2018, 8, 173.
[http://dx.doi.org/10.3389/fcimb.2018.00173] [PMID: 29888213]
[11]
Alberca, L.N.; Chuguransky, S.R.; Álvarez, C.L.; Talevi, A.; Salas-Sarduy, E. In silico guided drug repurposing: Discovery of new competitive and non-competitive inhibitors of falcipain-2. Front Chem., 2019, 7, 534.
[http://dx.doi.org/10.3389/fchem.2019.00534] [PMID: 31448257]
[12]
Price, H.P.; Güther, M.L.; Ferguson, M.A.; Smith, D.F. Myristoyl-CoA:protein N-myristoyltransferase depletion in trypanosomes causes avirulence and endocytic defects. Mol. Biochem. Parasitol., 2010, 169(1), 55-58.
[http://dx.doi.org/10.1016/j.molbiopara.2009.09.006] [PMID: 19782106]
[13]
Spinks, D.; Smith, V.; Thompson, S.; Robinson, D.A.; Luksch, T.; Smith, A.; Torrie, L.S.; McElroy, S.; Stojanovski, L.; Norval, S.; Collie, I.T.; Hallyburton, I.; Rao, B.; Brand, S.; Brenk, R.; Frearson, J.A.; Read, K.D.; Wyatt, P.G.; Gilbert, I.H. Development of small-molecule trypanosoma brucei n-myristoyltransferase Inhibitors: Discovery and optimisation of a novel binding mode. Chem-MedChem, 2015, 10(11), 1821-1836.
[http://dx.doi.org/10.1002/cmdc.201500301] [PMID: 26395087]
[14]
Frearson, J.A.; Brand, S.; McElroy, S.P.; Cleghorn, L.A.T.; Smid, O.; Stojanovski, L.; Price, H.P.; Guther, M.L.S.; Torrie, L.S.; Robinson, D.A.; Hallyburton, I.; Mpamhanga, C.P.; Brannigan, J.A.; Wilkinson, A.J.; Hodgkinson, M.; Hui, R.; Qiu, W.; Raimi, O.G.; van Aalten, D.M.F.; Brenk, R.; Gilbert, I.H.; Read, K.D.; Fairlamb, A.H.; Ferguson, M.A.J.; Smith, D.F.; Wyatt, P.G. Nmyristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature, 2010, 464(7289), 728-732.
[http://dx.doi.org/10.1038/nature08893] [PMID: 20360736]
[15]
Brand, S.; Norcross, N.R.; Thompson, S.; Harrison, J.R.; Smith, V.C.; Robinson, D.A.; Torrie, L.S.; McElroy, S.P.; Hallyburton, I.; Norval, S.; Scullion, P.; Stojanovski, L.; Simeons, F.R.C.; van Aalten, D.; Frearson, J.A.; Brenk, R.; Fairlamb, A.H.; Ferguson, M.A.J.; Wyatt, P.G.; Gilbert, I.H.; Read, K.D. Lead optimization of a pyrazole sulfonamide series of Trypanosoma brucei N-myristoyltransferase inhibitors: Identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human African trypanosomiasis. J. Med. Chem., 2014, 57(23), 9855-9869.
[http://dx.doi.org/10.1021/jm500809c] [PMID: 25412409]
[16]
Brand, S.; Cleghorn, L.A.T.; McElroy, S.P.; Robinson, D.A.; Smith, V.C.; Hallyburton, I.; Harrison, J.R.; Norcross, N.R.; Spinks, D.; Bayliss, T.; Norval, S.; Stojanovski, L.; Torrie, L.S.; Frearson, J.A.; Brenk, R.; Fairlamb, A.H.; Ferguson, M.A.J.; Read, K.D.; Wyatt, P.G.; Gilbert, I.H. Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors. J. Med. Chem., 2012, 55(1), 140-152.
[http://dx.doi.org/10.1021/jm201091t] [PMID: 22148754]
[17]
Panethymitaki, C.; Bowyer, P.W.; Price, H.P.; Leatherbarrow, R.J.; Brown, K.A.; Smith, D.F. Characterization and selective inhibition of myristoyl-CoA:protein N-myristoyltransferase from Trypanosoma brucei and Leishmania major. Biochem. J., 2006, 396(2), 277-285.
[http://dx.doi.org/10.1042/BJ20051886] [PMID: 16480339]
[18]
Gilbert, I.H. Drug discovery for neglected diseases: Molecular target-based and phenotypic approaches. J. Med. Chem., 2013, 56(20), 7719-7726.
[http://dx.doi.org/10.1021/jm400362b] [PMID: 24015767]
[19]
Brand, S.; Wyatt, Paul.; Thompson, S.; Smith, V.; Bayliss, T.; Harrison, J.; Norcross, N.; Cleghorn, L.; Gilbert, I.; Brenk, R. NMyristoyl transferase inhibitors. WO Patent 2010026365,, 2010 03March.
[20]
Perez-Llamas, C.; Lopez-Bigas, N. Gitools: Analysis and visualisation of genomic data using interactive heat-maps. PLoS One, 2011, 6(5), e19541.
[http://dx.doi.org/10.1371/journal.pone.0019541] [PMID: 21602921]
[21]
Golbraikh, A.; Shen, M.; Xiao, Z.; Xiao, Y.D.; Lee, K.H.; Tropsha, A. Rational selection of training and test sets for the development of validated QSAR models. J. Comput. Aided Mol. Des., 2003, 17(2-4), 241-253.
[http://dx.doi.org/10.1023/A:1025386326946] [PMID: 13677490]
[22]
Leonard, J.T.; Roy, K. On selection of training and test sets for the development of predictive QSAR Models. QSAR Comb. Sci., 2006, 25, 235-251.
[http://dx.doi.org/10.1002/qsar.200510161]
[23]
Martin, T.M.; Harten, P.; Young, D.M.; Muratov, E.N.; Golbraikh, A.; Zhu, H.; Tropsha, A. Does rational selection of training and test sets improve the outcome of QSAR modeling? J. Chem. Inf. Model., 2012, 52(10), 2570-2578.
[http://dx.doi.org/10.1021/ci300338w] [PMID: 23030316]
[24]
Torrie, L.S.; Wyllie, S.; Spinks, D.; Oza, S.L.; Thompson, S.; Harrison, J.R.; Gilbert, I.H.; Wyatt, P.G.; Fairlamb, A.H.; Frearson, J.A. Chemical validation of trypanothione synthetase: A potential drug target for human trypanosomiasis. J. Biol. Chem., 2009, 284(52), 36137-36145.
[http://dx.doi.org/10.1074/jbc.M109.045336] [PMID: 19828449]
[25]
Spinks, D.; Torrie, L.S.; Thompson, S.; Harrison, J.R.; Frearson, J.A.; Read, K.D.; Fairlamb, A.H.; Wyatt, P.G.; Gilbert, I.H. Design, synthesis and biological evaluation of Trypanosoma brucei trypanothione synthetase inhibitors. Chem. Med. Chem., 2012, 7(1), 95-106.
[http://dx.doi.org/10.1002/cmdc.201100420] [PMID: 22162199]
[26]
Oza, S.L.; Chen, S.; Wyllie, S.; Coward, J.K.; Fairlamb, A.H. ATP-dependent ligases in trypanothione biosynthesis--kinetics of catalysis and inhibition by phosphinic acid pseudopeptides. FEBS J., 2008, 275(21), 5408-5421.
[http://dx.doi.org/10.1111/j.1742-4658.2008.06670.x] [PMID: 18959765]
[27]
Leroux, A.E.; Krauth-Siegel, R.L. Thiol redox biology of trypanosomatids and potential targets for chemotherapy. Mol. Biochem. Parasitol., 2016, 206(1-2), 67-74.
[http://dx.doi.org/10.1016/j.molbiopara.2015.11.003] [PMID: 26592324]
[28]
Benítez, D.; Medeiros, A.; Fiestas, L.; Panozzo-Zenere, E.A.; Maiwald, F.; Prousis, K.C.; Roussaki, M.; Calogeropoulou, T.; Detsi, A.; Jaeger, T.; Šarlauskas, J.; Peterlin Mašič, L.; Kunick, C.; Labadie, G.R.; Flohé, L.; Comini, M.A. Identification of Novel Chemical Scaffolds Inhibiting Trypanothione Synthetase from Pathogenic Trypanosomatids. PLoS Negl. Trop. Dis., 2016, 10(4), e0004617.
[http://dx.doi.org/10.1371/journal.pntd.0004617] [PMID: 27070550]
[29]
Liñares, G.E.; Ravaschino, E.L.; Rodriguez, J.B. Progresses in the field of drug design to combat tropical protozoan parasitic diseases. Curr. Med. Chem., 2006, 13(3), 335-360.
[http://dx.doi.org/10.2174/092986706775476043] [PMID: 16475941]
[30]
Daunes, S.; D’Silva, C.; Kendrick, H.; Yardley, V.; Croft, S.L. QSAR study on the contribution of log P and E(s) to the in vitro antiprotozoal activity of glutathione derivatives. J. Med. Chem., 2001, 44(18), 2976-2983.
[http://dx.doi.org/10.1021/jm000502n] [PMID: 11520206]
[31]
D’Silva, C.; Daunes, S.; Rock, P.; Yardley, V.; Croft, S.L. Structure-activity study on the in vitro antiprotozoal activity of glutathione derivatives. J. Med. Chem., 2000, 43(10), 2072-2078.
[http://dx.doi.org/10.1021/jm990259w] [PMID: 10821719]
[32]
Jäger, T.; Flohé, L.; Schinzer, D. N5-substituted Benzo-2,3|azepino¬4,5-b|indol-6-ones for Treating Tropical Diseases. EP Patent 1 757 607 A1., 2007 28February.
[33]
Sarup, A.; Larsson, O.M.; Schousboe, A. GABA transporters and GABA-transaminase as drug targets. Curr. Drug Targets CNS Neurol. Disord., 2003, 2(4), 269-277.
[http://dx.doi.org/10.2174/1568007033482788] [PMID: 12871037]
[34]
Awad, R.; Muhammad, A.; Durst, T.; Trudeau, V.L.; Arnason, J.T. Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytother. Res., 2009, 23(8), 1075-1081.
[http://dx.doi.org/10.1002/ptr.2712] [PMID: 19165747]
[35]
Bansal, S.K.; Sinha, B.N.; Khosa, R.L. γ-amino butyric acid analogs as novel GABA-AT inhibitors: Molecular docking, synthesis and biological evaluation. Med. Chem. Res., 2013, 22, 134-146.
[http://dx.doi.org/10.1007/s00044-012-0023-0]
[36]
Choi, S.; Silverman, R.B. Inactivation and inhibition of γ-aminobutyric acid aminotransferase by conformationally restricted vigabatrin analogues. J. Med. Chem., 2002, 45(20), 4531-4539.
[http://dx.doi.org/10.1021/jm020134i] [PMID: 12238932]
[37]
Hawker, D.D.; Silverman, R.B. Synthesis and evaluation of novel heteroaromatic substrates of GABA aminotransferase. Bioorg. Med. Chem., 2012, 20(19), 5763-5773.
[http://dx.doi.org/10.1016/j.bmc.2012.08.009] [PMID: 22944334]
[38]
Krall, R.L.; Penry, J.K.; White, B.G.; Kupferberg, H.J.; Swinyard, E.A. Antiepileptic drug development: II. Anticonvulsant drug screening. Epilepsia, 1978, 19(4), 409-428.
[http://dx.doi.org/10.1111/j.1528-1157.1978.tb04507.x] [PMID: 699894]
[39]
Le, H.V.; Hawker, D.D.; Wu, R.; Doud, E.; Widom, J.; Sanishvili, R.; Liu, D.; Kelleher, N.; Silverman, R.B. Design and Mechanism of Tetrahydrothiophene-based GABA Aminotransferase inactivators. J. Am. Chem. Soc., 2015, 137, 4525-4533.
[http://dx.doi.org/10.1021/jacs.5b01155] [PMID: 25781189]
[40]
Lu, H.; Silverman, R.B. Fluorinated conformationally restricted γ-aminobutyric acid aminotransferase inhibitors. J. Med. Chem., 2006, 49(25), 7404-7412.
[http://dx.doi.org/10.1021/jm0608715] [PMID: 17149870]
[41]
Pan, Y.; Calvert, K.; Silverman, R.B. Conformationally-restricted vigabatrin analogs as irreversible and reversible inhibitors of γ-aminobutyric acid aminotransferase. Bioorg. Med. Chem., 2004, 12(21), 5719-5725.
[http://dx.doi.org/10.1016/j.bmc.2004.07.065] [PMID: 15465348]
[42]
Paslawski, T.; Knaus, E.; Iqbal, N.; Coutts, R.T.; Baker, G.B. B-phenylethylidenhydrazine, a novel inhibitor of GABA transaminase. Drug Dev. Res., 2001, 54, 35-39.
[http://dx.doi.org/10.1002/ddr.1202]
[43]
Patel, J.R.; Dholakiya, B.Z.; Mishra, N. In Vitro brain GABA-transaminase activity of 1-(4-acetylphenyl)-3-aryloxypyrrolidine-2,5-dione derivatives. J. Pharm. Res., 2013, 6, 442-446.
[http://dx.doi.org/10.1016/j.jopr.2013.04.012]
[44]
Pinto, A.; Tamborini, L.; Pennacchietti, E.; Coluccia, A.; Silvestri, R.; Cullia, G.; De Micheli, C.; Conti, P.; De Biase, D. Bicyclic γ-amino acids as inhibitors of γ-aminobutyrate aminotransferase. J. Enzyme Inhib. Med. Chem., 2016, 31(2), 295-301.
[http://dx.doi.org/10.3109/14756366.2015.1021251] [PMID: 25807299]
[45]
Qiu, J.; Silverman, R.B. A new class of conformationally rigid analogues of 4-amino-5-halopentanoic acids, potent inactivators of γ-aminobutyric acid aminotransferase. J. Med. Chem., 2000, 43(4), 706-720.
[http://dx.doi.org/10.1021/jm9904755] [PMID: 10691696]
[46]
Qume, M.; Fowler, L.J. Effect of chronic treatment with the GABA transaminase inhibitors γ-vinyl GABA and ethanolamine O-sulphate on the in vitro GABA release from rat hippocampus. Br. J. Pharmacol., 1997, 122(3), 539-545.
[http://dx.doi.org/10.1038/sj.bjp.0701383] [PMID: 9351512]
[47]
Ricci, L.; Frosini, M.; Gaggelli, N.; Valensin, G.; Machetti, F.; Sgaragli, G.; Valoti, M. Inhibition of rabbit brain 4-aminobutyrate transaminase by some taurine analogues: A kinetic analysis. Biochem. Pharmacol., 2006, 71(10), 1510-1519.
[http://dx.doi.org/10.1016/j.bcp.2006.02.007] [PMID: 16540097]
[48]
Sowa, B.; Rauw, G.; Davood, A.; Fassihi, A.; Knaus, E.E.; Baker, G.B. Design and biological evaluation of phenyl-substituted analogs of β-phenylethylidenehydrazine. Bioorg. Med. Chem., 2005, 13(14), 4389-4395.
[http://dx.doi.org/10.1016/j.bmc.2005.04.072] [PMID: 15927473]
[49]
Tao, Y.H.; Xu, H.B.; Yang, X.L. Inactivation of GABA transaminase by 3-chloro-1-(4-hydroxyphenyl)propan-1-one. Bioorg. Med. Chem. Lett., 2009, 19(3), 731-734.
[http://dx.doi.org/10.1016/j.bmcl.2008.12.033] [PMID: 19138517]
[50]
Tao, Y.H.; Xu, H.B.; Yang, X.L. Inactivation of GABA transaminase by 4-acryloylphenol. Bioorg. Med. Chem. Lett., 2006, 16(14), 3719-3722.
[http://dx.doi.org/10.1016/j.bmcl.2006.04.051] [PMID: 16690313]
[51]
Tao, Y.H.; Yuan, Z.; Tang, X.Q.; Xu, H.B.; Yang, X.L. Inhibition of GABA shunt enzymes’ activity by 4-hydroxybenzaldehyde derivatives. Bioorg. Med. Chem. Lett., 2006, 16(3), 592-595.
[http://dx.doi.org/10.1016/j.bmcl.2005.10.040] [PMID: 16290145]
[52]
Wang, Z.; Silverman, R.B. Syntheses and evaluation of fluorinated conformationally restricted analogues of GABA as potential inhibitors of GABA aminotransferase. Bioorg. Med. Chem., 2006, 14(7), 2242-2252.
[http://dx.doi.org/10.1016/j.bmc.2005.11.010] [PMID: 16314106]
[53]
Yuan, H.; Silverman, R.B. New substrates and inhibitors of γ-aminobutyric acid aminotransferase containing bioisosteres of the carboxylic acid group: Design, synthesis, and biological activity. Bioorg. Med. Chem., 2006, 14(5), 1331-1338.
[http://dx.doi.org/10.1016/j.bmc.2005.09.067] [PMID: 16263300]
[54]
Yuan, H.; Silverman, R.B. Structural modifications of (1S,3S)-3-amino-4-difluoromethylenecyclopentanecarboxylic acid, a potent irreversible inhibitor of GABA aminotransferase. Bioorg. Med. Chem. Lett., 2007, 17(6), 1651-1654.
[http://dx.doi.org/10.1016/j.bmcl.2006.12.119] [PMID: 17267220]
[55]
Zhao, L.X.; Park, J.G.; Moon, Y.S.; Basnet, A.; Choi, J.; Kim, E.K.; Jeong, T.C.; Jahng, Y.; Lee, E.S. Design, synthesis and anticonvulsive activity of analogs of γ-vinyl GABA. Farmaco, 2004, 59(5), 381-388.
[http://dx.doi.org/10.1016/j.farmac.2004.01.011] [PMID: 15120317]
[56]
Barton, M.E.; Klein, B.D.; Wolf, H.H.; White, H.S. Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy. Epilepsy Res., 2001, 47(3), 217-227.
[http://dx.doi.org/10.1016/S0920-1211(01)00302-3] [PMID: 11738929]
[57]
Ahsan, M.J.; Khalilullah, H.; Yasmin, S.; Jadav, S.S.; Stables, J.P.; Govindasamy, J. Synthesis and Anticonvulsant Evaluation of 2-(substituted benzylidene/ethylidene)-N-(substituted phenyl)hydrazine Carboxamide Analogues. Med. Chem. Res., 2013, 22, 2746-2754.
[http://dx.doi.org/10.1007/s00044-012-0271-z]
[58]
Ahsan, M.J.; Khalilullah, H.; Stables, J.P.; Govindasamy, J. Synthesis and anticonvulsant activity of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues. J. Enzyme Inhib. Med. Chem., 2013, 28(3), 644-650.
[http://dx.doi.org/10.3109/14756366.2012.663364] [PMID: 22397394]
[59]
Amir, M.; Ali, I.; Hassan, M.Z. Design, synthesis and anticonvulsant activity of some newer 3H-quinazolin-4-one derivatives. Indian J. Chem., 2014, 53B, 597-604.
[60]
Buenafe, O.E.; Orellana-Paucar, A.; Maes, J.; Huang, H.; Ying, X.; De Borggraeve, W.; Crawford, A.D.; Luyten, W.; Esguerra, C.V.; de Witte, P. Tanshinone IIA exhibits anticonvulsant activity in zebrafish and mouse seizure models. ACS Chem. Neurosci., 2013, 4(11), 1479-1487.
[http://dx.doi.org/10.1021/cn400140e] [PMID: 23937066]
[61]
Byrtus, H.; Obniska, J.; Czopek, A.; Kamiński, K.; Pawłowski, M. Synthesis and anticonvulsant activity of new N-Mannich bases derived from 5-cyclopropyl-5-phenyl- and 5-cyclopropyl-5-(4-chlorophenyl)-imidazolidine-2,4-diones. Bioorg. Med. Chem., 2011, 19(20), 6149-6156.
[http://dx.doi.org/10.1016/j.bmc.2011.08.017] [PMID: 21917466]
[62]
Coleman, N.; Nguyen, H.M.; Cao, Z.; Brown, B.M.; Jenkins, D.P.; Zolkowska, D.; Chen, Y.J.; Tanaka, B.S.; Goldin, A.L.; Rogawski, M.A.; Pessah, I.N.; Wulff, H. The riluzole derivative 2-amino-6-trifluoromethylthio-benzothiazole (SKA-19), a mixed KCa2 activator and NaV blocker, is a potent novel anticonvulsant. Neurotherapeutics, 2015, 12(1), 234-249.
[http://dx.doi.org/10.1007/s13311-014-0305-y] [PMID: 25256961]
[63]
Dawidowski, M.; Wilczek, M.; Kubica, K.; Skolmowski, M.; Turło, J. Structure-activity relationships of the aromatic site in novel anticonvulsant pyrrolo[1,2-a]pyrazine derivatives. Bioorg. Med. Chem. Lett., 2013, 23(22), 6106-6110.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.022] [PMID: 24095092]
[64]
Dawidowski, M.; Lewandowski, W.; Turło, J. Synthesis of new perhydropyrrolo[1,2-a]pyrazine derivatives and their evaluation in animal models of epilepsy. Molecules, 2014, 19(10), 15955-15981.
[http://dx.doi.org/10.3390/molecules191015955] [PMID: 25295751]
[65]
Dhayabaran, D.; Florance, E.J.; Nandakumar, K.; Shanmugarathinam, A.; Puratchikody, A. Anticonvulsant activity of fraction isolated from ethanolic extract of heartwood of Cedrus deodara. J. Nat. Med., 2014, 68(2), 310-315.
[http://dx.doi.org/10.1007/s11418-013-0798-4] [PMID: 23959538]
[66]
Florek-Luszczki, M.; Wlaź, A.; Luszczki, J.J. Interactions of levetiracetam with carbamazepine, phenytoin, topiramate and vigabatrin in the mouse 6Hz psychomotor seizure model - a type II isobolographic analysis. Eur. J. Pharmacol., 2014, 723, 410-418.
[http://dx.doi.org/10.1016/j.ejphar.2013.10.063] [PMID: 24211788]
[67]
Gasior, M.; Socała, K.; Nieoczym, D.; Wlaź, P. Clavulanic acid does not affect convulsions in acute seizure tests in mice. J. Neural Transm. (Vienna), 2012, 119(1), 1-6.
[http://dx.doi.org/10.1007/s00702-011-0662-1] [PMID: 21638029]
[68]
Gunia-Krzyak, A.; Waszkielewicz, A.M.; Soczyska, K.; Borczuch-Kostaska, M.; Cega, M.; Sataa, G.; Bojarski, A.J.; Marona, H. Synthesis and Anticonvulsant Activity of N-(trans)-3-phenylprop-2-en-1-yl (Cinnamyl). Derivatives of Aminoalkanols. Lett. Drug Des. Discov., 2014, 11, 1040-1052.
[http://dx.doi.org/10.2174/1570180811666140423203639]
[69]
Hebeisen, S.; Pires, N.; Loureiro, A.I.; Bonifácio, M.J.; Palma, N.; Whyment, A.; Spanswick, D.; Soares-da-Silva, P. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: A comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology, 2015, 89, 122-135.
[http://dx.doi.org/10.1016/j.neuropharm.2014.09.008] [PMID: 25242737]
[70]
Kamiński, K.; Obniska, J.; Chlebek, I.; Wiklik, B.; Rzepka, S. Design, synthesis and anticonvulsant properties of new N-Mannich bases derived from 3-phenylpyrrolidine-2,5-diones. Bioorg. Med. Chem., 2013, 21(21), 6821-6830.
[http://dx.doi.org/10.1016/j.bmc.2013.07.029] [PMID: 23993970]
[71]
Kamiński, K.; Wiklik, B.; Obniska, J. Synthesis and anticonvulsant activity of new N-phenyl-2-(4-phenylpiperazin-1-yl)acetamide derivatives. Med. Chem. Res., 2015, 24(7), 3047-3061.
[http://dx.doi.org/10.1007/s00044-015-1360-6] [PMID: 26167103]
[72]
Kumar, P.; Shrivastava, B.; Pandeya, S.N.; Tripathi, L.; Stables, J.P. Design, synthesis, and anticonvulsant evaluation of some novel 1,3-benzothiazol-2-yl hydrazones/acetohydrazones. Med. Chem. Res., 2012, 21, 2428-2442.
[http://dx.doi.org/10.1007/s00044-011-9768-0]
[73]
Luszczki, J.J.; Wlaź, A.; Marzeda, E.; Durmowicz, D.; Florek-Luszczki, M. Additive interaction of levetiracetam with lamotrigine in the mouse 6 Hz psychomotor seizure model– an Isobolographic Analysis. Curr. Issues Pharm. Med. Sci., 2013, 26, 82-87.
[74]
Mishra, R.K.; Baker, M.T. ortho Substituent effects on the anticonvulsant properties of 4-hydroxy-trifluoroethyl phenols. Bioorg. Med. Chem. Lett., 2012, 22(17), 5608-5611.
[http://dx.doi.org/10.1016/j.bmcl.2012.07.001] [PMID: 22840237]
[75]
Mishra, R.K.; Baker, M.T. Seizure prevention by the naturally occurring phenols, carvacrol and thymol in a partial seizure psychomotor model. Bioorg. Med. Chem. Lett., 2014, 24(23), 5446-5449.
[http://dx.doi.org/10.1016/j.bmcl.2014.10.028] [PMID: 25454269]
[76]
Pessah, N.; Yagen, B.; Hen, N.; Shimshoni, J.A.; Wlodarczyk, B.; Finnell, R.H.; Bialer, M. Design and pharmacological activity of glycinamide and N-methoxy amide derivatives of analogs and constitutional isomers of valproic acid. Epilepsy Behav., 2011, 22(3), 461-468.
[http://dx.doi.org/10.1016/j.yebeh.2011.08.026] [PMID: 21959082]
[77]
Nieoczym, D.; Socała, K.; Jedziniak, P.; Olejnik, M.; Wlaź, P. Effect of sildenafil, a selective phosphodiesterase 5 inhibitor, on the anticonvulsant action of some antiepileptic drugs in the mouse 6-Hz psychomotor seizure model. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2013, 47, 104-110.
[http://dx.doi.org/10.1016/j.pnpbp.2013.08.009] [PMID: 23994662]
[78]
Obniska, J.; Chlebek, I.; Kamiński, K. Synthesis and anticonvulsant properties of new mannich bases derived from 3,3-disubstituted pyrrolidine-2,5-diones. Part IV. Arch. Pharm. (Weinheim), 2012, 345(9), 713-722.
[http://dx.doi.org/10.1002/ardp.201200092] [PMID: 22674811]
[79]
Okoro, C.O.; Apraku, J.; Okoromoba, E.O.; Fadeyi, O.O. Synthesis and anticonvulsant activity of fluorinated cyclic enaminones. Lett. Drug Des. Discov., 2013, 10, 1024-1031.
[http://dx.doi.org/10.2174/15701808113109990064]
[80]
Orellana-Paucar, A.M.; Afrikanova, T.; Thomas, J.; Aibuldinov, Y.K.; Dehaen, W.; de Witte, P.A.M.; Esguerra, C.V. Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy. PLoS One, 2013, 8(12), e81634.
[http://dx.doi.org/10.1371/journal.pone.0081634] [PMID: 24349101]
[81]
Rivara, M.; Zuliani, V. In Vivo screening of diarylimidazoles as anticonvulsant agents. Med. Chem. Res., 2012, 21, 3428-3434.
[http://dx.doi.org/10.1007/s00044-011-9869-9]
[82]
Shaikh, M.F.; Tan, K.N.; Borges, K. Anticonvulsant screening of luteolin in four mouse seizure models. Neurosci. Lett., 2013, 550, 195-199.
[http://dx.doi.org/10.1016/j.neulet.2013.06.065] [PMID: 23851253]
[83]
Shandra, A.; Shandra, P.; Kaschenko, O.; Matagne, A.; Stöhr, T. Synergism of lacosamide with established antiepileptic drugs in the 6-Hz seizure model in mice. Epilepsia, 2013, 54(7), 1167-1175.
[http://dx.doi.org/10.1111/epi.12237] [PMID: 23750855]
[84]
Shekh-Ahmad, T.; Mawasi, H.; McDonough, J.H.; Finnell, R.H.; Wlodarczyk, B.J.; Yavin, E.; Bialer, M. Enantioselective pharmacodynamic and pharmacokinetic analysis of two chiral CNS-active carbamate derivatives of valproic acid. Epilepsia, 2014, 55(12), 1944-1952.
[http://dx.doi.org/10.1111/epi.12857] [PMID: 25442425]
[85]
Tosh, D.K.; Paoletta, S.; Deflorian, F.; Phan, K.; Moss, S.M.; Gao, Z.G.; Jiang, X.; Jacobson, K.A. Structural sweet spot for A1 adenosine receptor activation by truncated (N)-methanocarba nucleosides: Receptor docking and potent anticonvulsant activity. J. Med. Chem., 2012, 55(18), 8075-8090.
[http://dx.doi.org/10.1021/jm300965a] [PMID: 22921089]
[86]
Tripathi, L.; Kumar, P. Augmentation of GABAergic neurotransmission by novel N-(substituted)-2-[4-(substituted)benzylidene]-hydrazinecarbothioamides-a potential anticonvulsant approach. Eur. J. Med. Chem., 2013, 64, 477-487.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.019] [PMID: 23676307]
[87]
Tripathi, L.; Kumar, P.; Singh, R.; Stables, J.P. Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides. Eur. J. Med. Chem., 2012, 47(1), 153-166.
[http://dx.doi.org/10.1016/j.ejmech.2011.10.038] [PMID: 22082834]
[88]
Ulloora, S.; Shabaraya, R.; Ranganathan, R.; Adhikari, A.V. Synthesis, anticonvulsant and anti-inflammatory studies of new 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones. Eur. J. Med. Chem., 2013, 70, 341-349.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.010] [PMID: 24177360]
[89]
Wang, D.D.; Englot, D.J.; Garcia, P.A.; Lawton, M.T.; Young, W.L. Minocycline- and tetracycline-class antibiotics are protective against partial seizures in vivo. Epilepsy Behav., 2012, 24(3), 314-318.
[http://dx.doi.org/10.1016/j.yebeh.2012.03.035] [PMID: 22579030]
[90]
White, H.S.; Alex, A.B.; Pollock, A.; Hen, N.; Shekh-Ahmad, T.; Wilcox, K.S.; McDonough, J.H.; Stables, J.P.; Kaufmann, D.; Yagen, B.; Bialer, M. A new derivative of valproic acid amide possesses a broad-spectrum antiseizure profile and unique activity against status epilepticus and organophosphate neuronal damage. Epilepsia, 2012, 53(1), 134-146.
[http://dx.doi.org/10.1111/j.1528-1167.2011.03338.x] [PMID: 22150444]
[91]
Zolkowska, D.; Dhir, A.; Krishnan, K.; Covey, D.F.; Rogawski, M.A. Anticonvulsant potencies of the enantiomers of the neurosteroids androsterone and etiocholanolone exceed those of the natural forms. Psychopharmacology (Berl.), 2014, 231(17), 3325-3332.
[http://dx.doi.org/10.1007/s00213-014-3546-x] [PMID: 24705905]
[92]
El Habib Daho, M.; Amine Chikh, M. Combining bootstrapping samples, random subspaces and random forests to build classifiers. J. Med. Imaging Health Inform., 2015, 5, 539-544.
[http://dx.doi.org/10.1166/jmihi.2015.1423]
[93]
Vyskovsky, R.; Schwarz, D.; Janousova, E.; Kasparek, T. Random Subspace Ensemble Artificial Neural Networks for First-episode Schizophrenia Classification. In: Proc. 2016 Federated Conf. Comp. Sci. Info. Syst., FedCSIS; , 2016; pp. 317-321.
[94]
Toropova, A.P.; Toropov, A.A. CORAL: Binary classifications (active/inactive) for drug-induced liver injury. Toxicol. Lett., 2017, 268, 51-57.
[http://dx.doi.org/10.1016/j.toxlet.2017.01.011] [PMID: 28111161]
[95]
Gramatica, P. On the development and validation of QSAR models. Methods Mol. Biol., 2013, 930, 499-526.
[http://dx.doi.org/10.1007/978-1-62703-059-5_21] [PMID: 23086855]
[96]
Roy, K.; Mitra, I. On various metrics used for validation of predictive QSAR models with applications in virtual screening and focused library design. Comb. Chem. High Throughput Screen., 2011, 14(6), 450-474.
[http://dx.doi.org/10.2174/138620711795767893] [PMID: 21521150]
[97]
Carbonneau, M.A.; Granger, E.; Raymond, A.J. Gagnon, Ghyslain. Robust multiple-instance learning ensembles using random subspace instance selection. Pattern Recognit., 2016, 58, 83-99.
[http://dx.doi.org/10.1016/j.patcog.2016.03.035]
[98]
Min, S.H. A genetic algorithm-based heterogeneous random subspace ensemble model for bankruptcy prediction. Int. J. Appl. Eng. Res., 2016, 11, 2937-2931.
[99]
Zhang, Q.; Muegge, I. Scaffold hopping through virtual screening using 2D and 3D similarity descriptors: Ranking, voting, and consensus scoring. J. Med. Chem., 2006, 49(5), 1536-1548.
[http://dx.doi.org/10.1021/jm050468i] [PMID: 16509572]
[100]
Robin, X.; Turck, N.; Hainard, A.; Tiberti, N.; Lisacek, F.; Sanchez, J.C.; Müller, M. pROC: An open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformat., 2011, 12, 77.
[http://dx.doi.org/10.1186/1471-2105-12-77] [PMID: 21414208]
[101]
Truchon, J.F.; Bayly, C.I. Evaluating virtual screening methods: Good and bad metrics for the “early recognition” problem. J. Chem. Inf. Model., 2007, 47(2), 488-508.
[http://dx.doi.org/10.1021/ci600426e] [PMID: 17288412]
[102]
Mysinger, M.M.; Carchia, M.; Irwin, J.J.; Shoichet, B.K. Directory of useful decoys, enhanced (DUD-E): Better ligands and decoys for better benchmarking. J. Med. Chem., 2012, 55(14), 6582-6594.
[http://dx.doi.org/10.1021/jm300687e] [PMID: 22716043]

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