Understanding the comparative molecular field analysis (CoMFA) in terms of molecular quantum similarity and DFT-based reactivity descriptors

  • Alejandro Morales-Bayuelo
  • Ricardo A. Matute
  • Julio Caballero
Original Paper
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Accepted:

Abstract

The three-dimensional quantitative structure-activity relationship (3D QSAR) models have many applications, although the inherent complexity to understand the results coming from 3D-QSAR arises the necessity of new insights in the interpretation of them. Hence, the quantum similarity field as well as reactivity descriptors based on the density functional theory were used in this work as a consistent approach to better understand the 3D-QSAR studies in drug design. For this purpose, the quantification of steric and electrostatic effects on a series of bicycle [4.1.0] heptane derivatives as melanin-concentrating hormone receptor 1 antagonists were performed on the basis of molecular quantum similarity measures. The maximum similarity superposition and the topo-geometrical superposition algorithms were used as molecular alignment methods to deal with the problem of relative molecular orientation in quantum similarity. In addition, a chemical reactivity analysis using global and local descriptors such as chemical hardness, softness, electrophilicity, and Fukui functions, was developed. Overall, our results suggest that the application of this methodology in drug design can be useful when the receptor is known or even unknown.

Keywords

Chemical reactivity descriptors Comparative molecular field analysis (CoMFA) Density functional theory (DFT) Melanin-concentrating hormone receptor 1 (MCH-R1) Molecular quantum similarity (MQS) 3D-QSAR 
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Notes

Acknowledgments

Thanks to the Universidad de Talca (CBSM)) for the continuous support to this investigation, to the postdoctoral project N0 3150035 (FONDECYT, CHILE), to Dr. Ramon Carbó-Dorca (Universitat de Girona, España), and finally Dr. Andrzej Sokalski (associate editor) for their important comments.

Supplementary material

894_2015_2690_MOESM1_ESM.doc (107 kb)
ESM 1 (DOC 107 kb)

References

  1. 1.
    Bohm M, Sturzebecher J, Klebe G (1999) J Med Chem 42:458CrossRefGoogle Scholar
  2. 2.
    (1999) Nobel lecture: electronic structure of matter—wave functions and density functionals. Rev Mod Phys 71, No. 5Google Scholar
  3. 3.
    Amat L, Carbó-Dorca R, Ponec R (1999) J Med Chem 42:5169CrossRefGoogle Scholar
  4. 4.
    Klebe G (1998) Comparative molecular similarity indices: CoMSIA. In: Kubinyi H, Folkers G, Martin YC (eds) 3D QSAR in drug design, vol 3. Kluwer, London, p 87Google Scholar
  5. 5.
    World Health Organization. Obesity and overweight. Consulted January 20, 2014. http://www.who.int/mediacentre/factsheets/fs311/en/index.html. Reported in April 8, 2014.
  6. 6.
    Bleich S, Cutler D, Murray C, Adams A (2008) Annu Rev Public Health 29:273CrossRefGoogle Scholar
  7. 7.
    Martinez JA (2000) Body-weight regulation: causes of obesity. Proc Nutr Soc 59:337CrossRefGoogle Scholar
  8. 8.
    Bittencourt JC, Presse F, Arias C, Peto C, Vaughan J, Nahon JL, Vale W, Sawchenko PE (1992) J Comp Neurol 319:218CrossRefGoogle Scholar
  9. 9.
    Drewnowski A, Specter SE (2004) Am J Clin Nutr 79:6Google Scholar
  10. 10.
    Fernandez-Lopez J, Remesar X, Foz M, Alemany M (2002) For a review of current approaches for the treatment of obesity. Drugs 62:915CrossRefGoogle Scholar
  11. 11.
    James WP (2008) Obes Rev 9:6CrossRefGoogle Scholar
  12. 12.
    Nestle M, Jacobson MF (2000) Public Health Rep 115:12CrossRefGoogle Scholar
  13. 13.
    Sturm R (2007) Public Health 121:492CrossRefGoogle Scholar
  14. 14.
    Wang S, Behan J, O’Neill K, Weig B, Fried S, Laz T, Bayne M, Gustafson E, Hawes BE (2001) J Biol Chem 276:34664CrossRefGoogle Scholar
  15. 15.
    Sailer AW, Sano H, Zeng Z, McDonald TP, Pan J, Pong S-S, Feighner SD, Tan CP, Fukami T, Iwaasa H, Hreniuk DL, Morin NR, Sadowski SJ, Ito M, Bansa A, Ky B, Figueroa DJ, Jiang Q, Austin CP, MacNeil DJ, Ishihara A, Ihara M, Kanatani A, Van der Ploeg LHT, Howard AD, Liu Q (2001) Proc Natl Acad Sci 98:7564CrossRefGoogle Scholar
  16. 16.
    Chambers J, Ames RS, Bergsma D, Muir A, Fitzgerald LR, Hervieu G, Dytko GM, Foley JJ, Martin J, Liu W-S, Park J, Ellis C, Ganguly S, Cluderay SJ, Leslie RWS, Sarau HM (1999) Nature 400:261CrossRefGoogle Scholar
  17. 17.
    Xu R, Li S, Paruchova J, McBriar MD, Guzik H, Palani A, Clader JW, Cox K, Greenlee WJ, Hawes BE, Kowalski TJ, O’Neil K, Spar BD, Weig B, Weston DJ (2006) Bioorg Med Chem 14:3285CrossRefGoogle Scholar
  18. 18.
    Amat L, Carbó-Dorca R (2002) Int J Quantum Chem 87:59CrossRefGoogle Scholar
  19. 19.
    Geerlings P, De Proft F, Langenaeker W (2003) Chem Rev 103:1793CrossRefGoogle Scholar
  20. 20.
    Parr RG, Yang W (1989) Density Functional Theory of Atoms and Compounds. Oxford University Press, New YorkGoogle Scholar
  21. 21.
    Ayers PW, Anderson JSM, Bartolotti LJ (2005) Int J Quantum Chem 101:520CrossRefGoogle Scholar
  22. 22.
    Carbó-Dorca R, Arnau M, Leyda L (1980) Int J Quantum Chem 17:1185CrossRefGoogle Scholar
  23. 23.
    Carbó-Dorca R, Gironés X (2005) Int J Quantum Chem 101:8CrossRefGoogle Scholar
  24. 24.
    Gironés X, Carbó-Dorca R (2006) QSAR Comb Sci 25:579CrossRefGoogle Scholar
  25. 25.
    Bultinck P, Gironés X, Carbó-Dorca R (2005) Rev Comput Chem 21:127Google Scholar
  26. 26.
    Morales-Bayuelo A, Hernan A, Vivas-Reyes R (2010) Eur J Med Chem 45:4509CrossRefGoogle Scholar
  27. 27.
    Hirshfeld FL (1977) Theor Chim Acta 44:129CrossRefGoogle Scholar
  28. 28.
    De Proft F, Van Alsenoy C, Peeters A, Langenaeker W, Geerlings P (2002) J Comput Chem 23:1198CrossRefGoogle Scholar
  29. 29.
    Randic M, Johnson MA, Maggiora GM (1990) In concepts and applications of molecular similarity, design of compounds with desired properties. Wiley, New York. 77.Google Scholar
  30. 30.
    Boon G, Van Alsenoy C, De Proft F, Bultinck P, Geerlings P (2005) J Mol Struct 727:49CrossRefGoogle Scholar
  31. 31.
    Pearson RG (1997) Chemical hardness: applications from compounds to solids. Wiley-VHC, WeinheimCrossRefGoogle Scholar
  32. 32.
    Yang WT, Parr RG (1985) Proc Natl Acad Sci 82:6723CrossRefGoogle Scholar
  33. 33.
    Ayers P, Parr RG (2000) J Am Chem Soc 122:2010CrossRefGoogle Scholar
  34. 34.
    Parr RG, Yang W (1984) J Am Chem Soc 106:4049CrossRefGoogle Scholar
  35. 35.
    Fuentealba P, Pérez P, Contreras R (2000) J Chem Phys 113:2544CrossRefGoogle Scholar
  36. 36.
    Galván M, Pérez P, Contreras R, Fuentealba P (1999) Chem Phys Lett 30:405Google Scholar
  37. 37.
    Mortier WJ, Yang W (1986) J Am Chem Soc 108:5708CrossRefGoogle Scholar
  38. 38.
    Blankley CJ (1996) In: van de Waterbeemd H (ed) Structure property correlations in drug research. Academic, Austin, pp 111–177Google Scholar
  39. 39.
    Cramer RD III, Patterson DE, Bunce JD (1988) J Am Chem Soc 110:5959–5967CrossRefGoogle Scholar
  40. 40.
    Constans P, Amat L, Carbó-Dorca R (1997) J Comput Chem 18:826CrossRefGoogle Scholar
  41. 41.
    Girones X, Robert D, Carbó-Dorca R (2001) J Comput Chem 22:255CrossRefGoogle Scholar
  42. 42.
    Morales-Bayuelo A, Torres J, Vivas-Reyes R (2012) J Theor Comput Chem 11:1CrossRefGoogle Scholar
  43. 43.
    Morales-Bayuelo A, Vivas-Reyes R (2013) J Math Chem 51:125CrossRefGoogle Scholar
  44. 44.
    Morales-Bayuelo A, Vivas-Reyes R (2014) J Quant Chem Article ID 239845, 19 pagesGoogle Scholar
  45. 45.
    Morales-Bayuelo A, Vivas-Reyes R (2014) J Quant Chem Article ID 850163, 12 pagesGoogle Scholar
  46. 46.
    Besalú E, Gironés X, Amat L, Carbó-Dorca R (2002) Acc Chem Res 35:289CrossRefGoogle Scholar
  47. 47.
    Becke AD (1988) Phys Rev A 38:3098CrossRefGoogle Scholar
  48. 48.
    Lee C, Yang W, Parr RG (1988) Phys Rev B 37:785CrossRefGoogle Scholar
  49. 49.
    Vosko SH, Wilk L, Nusair M (1980) Can J Phys 58:1200CrossRefGoogle Scholar
  50. 50.
    Katritzky AR, Akhmedov NG, Doskocz J, Mohapatra PP, Hall D, Güven A (2007) Magn Reson Chem 45:532CrossRefGoogle Scholar
  51. 51.
    Bultinck P, Clarisse D, Ayers P, Carbó-Dorca R (2011) Phys Chem Chem Phys 13:6110CrossRefGoogle Scholar
  52. 52.
    Morales-Bayuelo A, Caballero J (2015) J Mol Model 21:45CrossRefGoogle Scholar
  53. 53.
    Frisch MJ, G. Trucks W, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Jr. Montgomery JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2010) Gaussian 09, Revision C.01. Gaussian Inc, Wallingford, CTGoogle Scholar
  54. 54.
    Constans P, Amat L, Carbó-Dorca R (1997) J Comput Chem 18:826CrossRefGoogle Scholar
  55. 55.
    Girones X, Robert D, Carbó-Dorca R (2001) J Comput Chem 22:255CrossRefGoogle Scholar
  56. 56.
    Dyck B, Markison S, Zhao L, Tamiya J, Grey J, Rowbottom MW, Zhang M, Vickers T, Sorensen K, Norton C, Wen J, Heise CE, Saunders J, Conlon P, Madan A, Schwarz D, Goodfellow VS (2006) J Med Chem 49:3753CrossRefGoogle Scholar
  57. 57.
    Cirauqui N, Schrey AK, Galiano S, Ceras J, Pérez-Silanes S, Aldana I, Monge A, Kühne R (2010) Bioorg Med Chem 18:7365CrossRefGoogle Scholar
  58. 58.
    MCH-R1 melanin-concentrating hormone receptor 1 (Homo sapiens). http://www.ncbi.nlm.nih.gov/sites/entrez Gene ID: 2847, updated on 14-01-2015
  59. 59.
    Cheon HG (2012) Handb Exp Pharmacol 209:383Google Scholar
  60. 60.
    Hervieu G (2003) Expert Opin Ther Targets 7:495CrossRefGoogle Scholar
  61. 61.
    Hervieu GJ (2006) Expert Opin Ther Targets 10:211CrossRefGoogle Scholar
  62. 62.
    Huttunen R, Syrjänen J (2013) Int J Obes 37:333CrossRefGoogle Scholar
  63. 63.
    Rivera G, Bocanegra-García V, Galiano S, Cirauqui N, Ceras J, Pérez S, Aldana I, Monge A (2008) Curr Med Chem 15:1025CrossRefGoogle Scholar
  64. 64.
    Saito Y, Maruyama K (2006) J Exp Zool Comp Exp Biol 305:761CrossRefGoogle Scholar
  65. 65.
    Shimazaki T, Yoshimizu T, Chaki S (2006) CNS Drugs 20:801CrossRefGoogle Scholar
  66. 66.
    Su J, McKittrick BA, Tang H, Czarniecki M, Greenlee WJ, Hawes BE, O’Neill K (2005) Bioorg Med Chem 5:1829CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Alejandro Morales-Bayuelo
    • 1
  • Ricardo A. Matute
    • 2
  • Julio Caballero
    • 1
  1. 1.Centro de Bioinformática y Simulación Molecular (CBSM)Universidad de TalcaTalcaChile
  2. 2.Departamento de Química, Facultad de CienciasUniversidad de ChileSantiagoChile

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