Skip to main content
SpringerLink
Log in

QSAR Approach in Study of Mutagenicity of Aromatic and Heteroaromatic Amines

  • Chapter
  • First Online:
QSAR and Molecular Modeling Studies in Heterocyclic Drugs II

Part of the book series: Topics in Heterocyclic Chemistry ((TOPICS,volume 4))

Abstract

In this chapter we give an overview on QSAR models for treating the mutagenicity of cyclic amines. An extensive discussion is focused on the topological, E-state, quantum chemical, and empirical descriptors (logP) that are often used in corresponding models. Two case studies are presented in more detail. The conclusion addresses the OECD principles for validation of models that are used for regulatory purposes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

(Q)SAR:

(Quantitative) structure–activity relationship

E HOMO :

Energy of the highest occupied orbital

E LUMO :

Energy of the lowest unoccupied orbital

2D, 3D:

Two dimensional, Three dimensional

OECD:

Organization for economic cooperation and development

References

  1. Benigni R, Giuliani A, Franke R, Gruska A (2000) Chem Rev 100:3697

    Article  CAS  Google Scholar 

  2. McCann J, Choi E, Yamasaki E, Ames BN (1975) Proc Natl Acad Sci USA 72:5135

    Article  CAS  Google Scholar 

  3. Zeiger E (2001) Mutat Res 492:29

    CAS  Google Scholar 

  4. Dolin PJ (1992) Br J Cancer 65:476

    Article  CAS  Google Scholar 

  5. Vincis P, Pirastu R (1997) Cancer Cause Control 8:346

    Article  Google Scholar 

  6. Kinosita R (1937) Tr Soc Path Jap 27:665

    Google Scholar 

  7. Benigni R, Giuliani A, Gruska A, Franke R (2003) QSARs for the mutagenicity and carcinogenicity of the aromatic amines. In: Benigni R (ed) Quantitative structure–activity relationship (QSAR) models of mutagens and carcinogens. CRC, Boca Raton FL, p 125

    Google Scholar 

  8. Benigni R (2005) Chem Rev 105:1767

    Article  CAS  Google Scholar 

  9. Klopman G, Frierson MR, Rosenkranz HS (1985) Environ Mutagen 7:625

    Article  CAS  Google Scholar 

  10. Zhang YP, Klopman G, Rosenkranz HS (1993) Environ Mol Mutagen 21:100

    Article  CAS  Google Scholar 

  11. Glende C, Klein M, Schmitt H, Erdinger L, Boche G (2002) Mutat Res 515:15

    CAS  Google Scholar 

  12. Debnath AK, Debnath G, Shusterman AJ, Hansh C (1992) Environ Mol Mutagen 19:37

    Article  CAS  Google Scholar 

  13. Garg A, Bhat KL, Bock CW (2002) Dyes Pigments 55:35

    Article  CAS  Google Scholar 

  14. CODESSATM, v20, Semichem, 7204 Mullen, Shawnee KS 66216, USA

    Google Scholar 

  15. Gramatica P, Connsonni V, Pavan M (2003) SAR QSAR Environ Res 14:237

    Article  CAS  Google Scholar 

  16. Todeschini R, Consonni V, Mauri A, Pavan M (2002) DRAGON rel 2.1 for Windows, Milano, Italy

    Google Scholar 

  17. Todeschini R, Mauri A (2000) DOLPHIN rel 2.1 for Windows, Milano, Italy

    Google Scholar 

  18. Leardi R, Boggia R, Terrile M (1992) J Chemom 6:267

    Article  CAS  Google Scholar 

  19. Chung KT, Chen SC, Wong TY, Li YS, Wei CI, Chou MW (2000) Toxicol Sci 56:351

    Article  CAS  Google Scholar 

  20. Hatch FT, Lightstone, Colvin ME (2000) Environ Mol Mutagen 35:279

    Article  CAS  Google Scholar 

  21. Patlewicz G, Rodford R, Walker JD (2003) Environ Toxicol Chem 22:1885

    Article  CAS  Google Scholar 

  22. Votano JR, Parham M, Hall LH, Kier LB, Oloff S, Tropsha A, Xie Q, Tong W (2004) Mutagenesis 19:365

    Article  CAS  Google Scholar 

  23. Lozano JJ, Pastor M, Cruciani G, Gaedt K, Centeno NB, Gago F, Sanz F (2000) J Comput Aid Mol Des 14:341

    Article  CAS  Google Scholar 

  24. Mattioni BE, Kauffman GW, Jurs PC, Custer LL, Durham SK, Pearl GM (2003) J Chem Inf Comput Sci 43:949

    Article  CAS  Google Scholar 

  25. Contrera JF, Matthews EJ, Kruhlak NL, Benz RD (2005) Regul Toxicol Pharmacol 43:313

    Article  CAS  Google Scholar 

  26. Zupan J, Vračko M, Novič M (2000) Acta Chim Slov 47:11

    Google Scholar 

  27. Todeschini R, Consonni V (2000) The handbook of molecular descriptors. Wiley, New York

    Book  Google Scholar 

  28. Schuur JH, Selzer P, Gasteiger J (1996) J Chem Inf Comput Sci 36:334

    Article  CAS  Google Scholar 

  29. Diudea MV (ed) (2001) QSPR/QSAR studies by molecular descriptors. Nova Science, Hungtington, New York

    Google Scholar 

  30. Basak SC, Mills D (2001) SAR QSAR Environ Res 12:481

    Article  CAS  Google Scholar 

  31. Wiener H (1947) J Am Chem Soc 69:2636

    Article  CAS  Google Scholar 

  32. Balaban A (2001) A personal view about topological indices for QSAR/QSPR. In: Diudea MV (ed) QSPR/QSAR studies by molecular descriptors. Nova Science, Hungtington, New York

    Google Scholar 

  33. Devillers J, Balaban AT (eds) (1999) Topological indices and related descriptors in QSAR and QSPR. Gordon and Breach, Reading, UK

    Google Scholar 

  34. Randić M (1998) Topological indices. In: Schleyer PvR, Allinger NL, Clark T, Gasteiger J, Kollman PA, Schaefer III HF, Schreiner PR (eds) Encyclopedia of computational chemistry. Wiley, Chichester

    Google Scholar 

  35. Netzeva TI (2004) Whole molecule and atom-based topological descriptors. In: Cronin MTD (ed) Predicting chemical toxicity and fate. CRC, Boca Raton FL

    Google Scholar 

  36. Randič M (1975) J Am Chem Soc 97:6609

    Article  Google Scholar 

  37. Randič M (2001) J Mol Graphics Modelling 20:19

    Article  Google Scholar 

  38. Kier LB, Hall LH (1976) J Pharm Sci 65:1806

    Article  CAS  Google Scholar 

  39. Rose K, Hall LH, Kier LB (2002) J Chem Inf Comput Sci 42:651

    Article  CAS  Google Scholar 

  40. Katritzky AR, Lobanov VS, Karelson M (1994) CODESSA Reference manual 2.0, Gainesville

    Google Scholar 

  41. Rohrbaugh RH, Jurs PC (1987) Anal Chim Acta 199:99

    Article  CAS  Google Scholar 

  42. Randić M, Razinger M (1997) On characterization of 3D molecular structure. In: Balaban AT (ed) From chemical topology to three-dimensional structure. Plenum, New York

    Google Scholar 

  43. Thouless DJ (1972) The quantum mechanics of many-body systems. Academic, New York

    Google Scholar 

  44. Schaefer III HF (1977) Methods of electronic structure theory. Plenum, New York

    Google Scholar 

  45. Hehre WJ, Radom L, Schleyer PR, Pople JA (1986) Ab initio molecular orbital theory. Wiley, New York

    Google Scholar 

  46. Murrell JN, Herget AJ (1972) Semi-empirical self-consistent-field-molecular theory of molecules. Wiley, New York

    Google Scholar 

  47. Koopmans T (1934) Physica 1:104

    Article  Google Scholar 

  48. Schüürmann G (2004) Quantum chemical descriptors in structure–activity relationships – calculation, interpretation, and comparison of methods. In: Cronin MTD (ed) Predicting chemical toxicity and fate. CRC, Boca Raton FL

    Google Scholar 

  49. Hansch C, Maloney PP, Fujita T, Muir RM (1962) Nature 194:178

    Article  CAS  Google Scholar 

  50. Silverman RB (2004) The organic chemistry of drug design and drug action. Elsevier, Amsterdam, p 55

    Google Scholar 

  51. Medić-Šarić M, Mornar A, Badovinac-Črbjević T, Jasprica I (2004) Croat Chem Acta 1–2:367

    Google Scholar 

  52. Petrauskas AA, Kolovanov EA (2000) Perspect. Drug Discovery and Design 19:99

    Article  CAS  Google Scholar 

  53. Eros D, Kovesdi I, Orfi L, Takacs-Novak K, Acsady G, Keri G (2002) Current Med Chem 9:1819

    CAS  Google Scholar 

  54. Schuur JH, Selzer P, Gasteiger J (1996) J Chem Inf Comput Sci 36:334

    Article  CAS  Google Scholar 

  55. Zupan J, Vračko M, Novič M (2000) Acta Chim Slov 47:19

    CAS  Google Scholar 

  56. Hemmer CM, Gasteiger J (2000) Anal Chim Acta 420:145

    Article  CAS  Google Scholar 

  57. Bursi R, Dao T, Wijk Tv, Gooyer Md, Kellenbach E, Verwer P (1999) J Chem Inf Comput Sci 39:861

    Article  CAS  Google Scholar 

  58. Cramer RD, DePriest SA, Patterson DE, Hecht P (1993) The developing practice of comparative molecular field analysis. In: Kubinyi H (ed) 3D QSAR in drug design theory, methods and applications, vol 1. ESCOM Leiden 443–485

    Google Scholar 

  59. http://www.ndsu.nodak.edu/qsar_soc/resource/software.htm

  60. Leardi R (ed) (2003) Nature-inspired methods in chemometrics: Genetic algorithms and artificial neural networks. Elsevier, Amsterdam

    Google Scholar 

  61. Helma C (ed) (2005) Predictive toxicology. Taylor Francis, Boca Raton FL

    Google Scholar 

  62. Zupan J, Gasteiger J (1999) Neural networks in chemistry and drug design. Wiley, Weinheim

    Google Scholar 

  63. Vračko M (2005) Curr Comput-Aided Drug Des 1:73

    Article  Google Scholar 

  64. Panek JJ, Jezierska A, Vračko M (2005) J Chem Inf Model 45:264

    Article  CAS  Google Scholar 

  65. Spycher S, Pellegrini E, Gasteiger J (2005) J Chem Inf Model 45:200

    Article  CAS  Google Scholar 

  66. Roncaglioni A, Novič M, Vračko M, Benfenati E (2004) J Chem Inf Comput Sci 44:300

    Article  CAS  Google Scholar 

  67. Jezierska A, Vračko M, Basak SC (2004) Mol Divers 8:371

    Article  CAS  Google Scholar 

  68. Shirai T, Sano M, Tamano S, Takahashi S, Hirose T, Futakuchi M, Hasegawa R, Imaida K, Matsumoto K-I, Wakabayashi K, Sugimura T, Ito N (1997) Cancer Res 57:195

    CAS  Google Scholar 

  69. Felton JS, Knize MG, Hatch FT, Tanga MJ, Colvin ME (1999) Cancer Letters 143:127

    Article  CAS  Google Scholar 

  70. Cash GG (2001) Mutat Res Genet Toxicol Environ Mutagen 491:31

    Article  CAS  Google Scholar 

  71. Cash GG, Anderson B, Mayo K, Bogaczyk S, Tunkel J (2005) Mutat Res 585:170

    CAS  Google Scholar 

  72. Maran U, Karelson M, Katritzky AR (1999) Quant Struct-Act Relat 18:3

    Article  CAS  Google Scholar 

  73. Karelson M, Sild S, Maran U (2000) Mol Simul 24:229

    Article  CAS  Google Scholar 

  74. Basak SC, Mills D (2001) SAR QSAR Environ Res 12:481

    Article  CAS  Google Scholar 

  75. Basak SC, Mills D, Balaban AT, Gute BD (2001) J Chem Inf Comput Sci 41:671

    Article  CAS  Google Scholar 

  76. Basak SC, Gute BD, Grunwald GD (1998) Relative effectiveness of topological, geometrical, and quantum chemical parameters in estimating mutagenicity of chemicals. In: Chen F, Schüürmann G (eds) Proceedings of the quantitative structure–activity relationships in environmental sciences. VII SETAC, Pensacola FL, p 245

    Google Scholar 

  77. Frisch MJ, Trucks GW, Schlegel HB, Gill PMW, Johnson BG, Robb MA, Cheeseman JR, Keith T, Petersson GA, Montgomery JA, Raghavachari K, Al-Laham MA, Zakrzewski VG, Ortiz JV, Foresman JB, Peng CY, Ayala PY, Chen W, Wong MW, Andres JL, Replogle ES, Gomperts R, Martin RL, Fox DJ, Binkley JS, Defrees DJ, Baker J, Stewart JP, Head-Gordon M, Gonzalez C, Pople JA (1995) GAUSSIAN 94. Gaussian Inc, Pittsburgh, PA

    Google Scholar 

  78. Vračko M, Szymoszek A, Barbieri P (2004) J Chem Inf Comput Sci 44:352

    Article  CAS  Google Scholar 

  79. Valkova I, Vračko M, Basak SC (2004) Anal Chim Acta 509:179

    Article  CAS  Google Scholar 

  80. Vračko M, Mills D, Basak SC (2004) Environ Toxicol Pharmacol 16:25

    Article  CAS  Google Scholar 

  81. MOLCONN-Z (2000) Version 3.5. Hall Associates, Quincy, MA

    Google Scholar 

  82. SAS Institute(1988) Release 6.03. Cary, NC

    Google Scholar 

  83. Golbraikh A, Tropsha A (2003) J Comput-aided Mol Des 16:357

    Article  Google Scholar 

  84. Golbraikh A (2000) J Chem Inf Comput Sci 40:414

    Article  CAS  Google Scholar 

  85. OECD series on testing and assessment, Number 12. ENV/JM/MONO(99)2

    Google Scholar 

  86. The principles for establishing the status of development and validation of (quantitative) structure–activity relationships [(Q)SARs]. OECD document ENV/JM/TG(2004)27

    Google Scholar 

  87. Snyder RD, Smith MD (2005) Drug Discov Today 10:1119

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Kemijski inštitut/National Institute of Chemistry, Hajdrihova 19, 1000, Ljubljana, Slovenia

    Marjan Vračko

Authors
  1. Marjan Vračko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marjan Vračko .

Editor information

Satya Prakash Gupta

Rights and permissions

Reprints and permissions

About this chapter

Cite this chapter

Vračko, M. QSAR Approach in Study of Mutagenicity of Aromatic and Heteroaromatic Amines. In: Gupta, S.P. (eds) QSAR and Molecular Modeling Studies in Heterocyclic Drugs II. Topics in Heterocyclic Chemistry, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7081_026

Download citation

Publish with us

Policies and ethics

Search

Navigation