Semi-correlations as a tool to build up categorical (active/inactive) model of GABAA receptor modulator activity

  • Alla P. ToropovaEmail author
  • Andrey A. Toropov
  • Emilio Benfenati
Original Research


The interpretation of mode of action for GABAA receptor modulator activity is an important task of medicinal chemistry. The computational elucidation of the modulator activity is one of the ways to solve the above task. So-called semi-correlation is a tool for prediction of GABAA receptor modulator activity. The semi-correlation is based on the Monte Carlo method. This approach is to build up categorical classification models into two classes: (i) active and (ii) inactive. The CORAL software ( can be used to build up the semi-correlations. The statistical quality of models (for external validation sets) based on semi-correlation has the range of Matthews correlation coefficient (MCC) is 0.72–1.00 for 30 random splits of all available data (n = 210) into the training and validation sets. In contrast to existing approaches, the predictive CORAL models give prediction using solely data on molecular architecture (represented by simplified molecular input-line entry system = SMILES) and available experimental data on endpoints. Suggested models for prediction of GABAA receptor modulator activity are built up according to the OECD principles. Thus, the approach based on the semi-correlation can be a useful tool for studying of the GABAA receptor modulators activity.


GABAA receptor Neuroprotection SAR Fuzzy set OECD principles CORAL software 



The project LIFE-CONCERT contract (LIFE17 GIE/IT/000461) for financially supported this.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11224_2018_1226_MOESM1_ESM.xlsx (33 kb)
ESM 1 (XLSX 32 kb)


  1. 1.
    Machado KDC, Oliveira GLDS, Islam MT, de Almeida AAC, Junior ALG, Machado KDC, de Sousa DP, Melo-Cavalcante AAC, de Freitas RM (2018). Chem Biol Interact 289:119–128CrossRefGoogle Scholar
  2. 2.
    Lees G, Coyne L, Zheng J, Nicholson RA (2004). Environ Toxicol Pharmacol 15:61–69CrossRefGoogle Scholar
  3. 3.
    Mohler H (2011). Neuropharmacology 60:1042–1049CrossRefGoogle Scholar
  4. 4.
    Tong F, Coats JR (2012). Pest Manag Sci 68:1122–1129CrossRefGoogle Scholar
  5. 5.
    Marder M, Estiú G, Blanch LB, Viola H, Wasowski C, Medina JH, Paladini AC (2001). Bioorg Med Chem 9:323–335CrossRefGoogle Scholar
  6. 6.
    Huang X, Liu T, Gu J, Luo X, Ji R, Cao Y, Xue H, Wong JTF, Wong BL, Pei G, Jiang H, Chen K (2001). J Med Chem 44:1883–1891CrossRefGoogle Scholar
  7. 7.
    Coecke S, Eskes C, Gartlon J, Kinsner A, Price A, van Vliet E, Prieto P, Boveri M, Bremer S, Adler S, Pellizzer C, Wendel A, Hartung T (2006). Environ Toxicol Pharmacol 21:153–167CrossRefGoogle Scholar
  8. 8.
    Toropova MA, Toropov AA, Raška I, Rašková M (2015). Comput Biol Med 64:148–154CrossRefGoogle Scholar
  9. 9.
    Silva MIG, Silva MAG, de Aquino Neto MR, Moura BA, de Sousa HL, de Lavor EPH, de Vasconcelos PF, Macêdo DS, de Sousa DP, Vasconcelos SMM, de Sousa FCF (2009). Fitoterapia 80:506–513CrossRefGoogle Scholar
  10. 10.
    Hutt A, Buhry L (2014). J Comput Neurosci 37:417–437CrossRefGoogle Scholar
  11. 11.
    McCarson KE, Enna SJ (2014). Neurochem Res 39:1948–1963CrossRefGoogle Scholar
  12. 12.
    Witkin JM, Cerne R, Wakulchik M, S J, Gleason SD, Jones TM, Li G, Arnold LA, Li JX, Schkeryantz JM, Methuku KR, Cook JM, Poe MM (2017). Pharmacol Biochem Behav 157:35–40CrossRefGoogle Scholar
  13. 13.
    Hendrie HC (1998). Am J Geriatr Psychiatry 6(2 SUPPL):S3–S18CrossRefGoogle Scholar
  14. 14.
    Sosa-Ortiz AL, Acosta-Castillo I, Prince MJ (2012). Arch Med Res 43:600–608CrossRefGoogle Scholar
  15. 15.
    Mar J, Soto-Gordoa M, Arrospide A, Moreno-Izco F, Martínez-Lage P (2015). Alzheimers Res Ther 7(1):art no 2CrossRefGoogle Scholar
  16. 16.
    Singhuber J, Baburin I, Ecker GF, Kopp B, Hering S (2011). Eur J Pharmacol 668:57–64CrossRefGoogle Scholar
  17. 17.
    Duchowicz PR, Vitale MG, Castro EA, Autino JC, Romanelli GP, Bennardi DO (2008). Eur J Med Chem 43:1593–1602CrossRefGoogle Scholar
  18. 18.
    Zhang W, Xia S, Ye J, Tang Y, Li Z, Zhu W, Cheng J (2013). Med Chem Res 22:5961–5972CrossRefGoogle Scholar
  19. 19.
    Yang Y, Zhang W, Cheng J, Tang Y, Peng Y, Li Z (2013). Chem Biol Drug Des 81:583–590CrossRefGoogle Scholar
  20. 20.
    Deeb O, Shaik B, Agrawal VK (2014). J Enzyme Inhib Med Chem 29:670–676CrossRefGoogle Scholar
  21. 21.
    Malek-Khatabi A, Kompany-Zareh M, Gholami S, Bagheri S (2014). Chemom Intell Lab Syst 135:157–165CrossRefGoogle Scholar
  22. 22.
    Waters L, Manchester KR, Maskell PD, Haegeman C, Haider S (2018). Sci Justice 58:219–225CrossRefGoogle Scholar
  23. 23.
    Boison A (2014) A thesis submitted to the Graduate School – Camden Rutgers, The State University of New Jersey, Camden, New Jersey. Accessed 19 Nov 2018
  24. 24.
    Mohabatkar H, Mohammad Beigi M, Esmaeili A (2011). J Theor Biol 281:18–23CrossRefGoogle Scholar
  25. 25.
    Jurik A, Reicherstorfer R, Zdrazil B, Ecker GF (2013). Mol Inf 32:415–419CrossRefGoogle Scholar
  26. 26.
    He D, Wang M, Zhao S, Shu Y, Zeng H, Xiao C, Lu C, Liu Y (2017). Fitoterapia 119:136–149CrossRefGoogle Scholar
  27. 27.
    Prachayasittikul V, Worachartcheewan A, Toropova AP, Toropov AA, Schaduangrat N, Prachayasittikul V, Nantasenamat C (2017). SAR QSAR Environ Res 28:1–16CrossRefGoogle Scholar
  28. 28.
    Worachartcheewan A, Prachayasittikul V, Toropova AP, Toropov AA, Nantasenamat C (2015) Molec. Divers 19:955–964Google Scholar
  29. 29.
    CORAL, Accessed 25 July 2018
  30. 30.
    Toropov AA, Toropova AP, Benfenati E, Dorne JL (2018). Chem Biol Interact 290:1–5CrossRefGoogle Scholar
  31. 31.
    Toropova AP, Toropov AA (2017). Toxicol Lett 275:57–66CrossRefGoogle Scholar
  32. 32.
    Toropov AA, Toropova AP, Marzo M, Dorne JL, Georgiadis N, Benfenati E (2017). Environ Toxicol Pharmacol 53:158–163CrossRefGoogle Scholar
  33. 33.
    Fatemi MH, Gharaghani S (2007) Bioorg Med Chem 15:7746–7754Google Scholar
  34. 34.
    Weininger D (1988) J Chem Inf Comput Sci 28:31-36CrossRefGoogle Scholar
  35. 35.
    Zadeh LA (1978) Fuzzy Sets Syst 1:3-28Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Environmental Health Science, Laboratory of Environmental Chemistry and ToxicologyIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly

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