Skip to main content
SpringerLink
Log in

A quantitative structure–activity relationship study of the skin-irritant effect of thietanes

  • Original Paper
  • Published:
Monatshefte für Chemie - Chemical Monthly Aims and scope Submit manuscript

Abstract

Quantitative structure–activity relationships (QSAR) have been used to study the skin-irritant effect of 84 thietanes. A suitable set of molecular descriptors was calculated and the important descriptors were selected with the aid of the genetic algorithm and stepwise multiple regression methods. On the basis of principal-components analysis the data set was divided into 67 molecules in a training set and 17 molecules in a test set. The models were validated by use of leave-one-out cross-validation, an external test set, and a Y-randomization test. Comparison of the results obtained indicated the superiority of the genetic algorithm over stepwise multiple regression for feature selection. One GA–MLR model with six selected descriptors was obtained. This model could be used to predict the skin-irritant effect of the thietanes, with high statistical significance (R 2training  = 0.897, Q 2LOO  = 0.872, Q 2LGO  = 0.800, F = 87.253, R 2test  = 0.921). The results suggest that the number of bonds in the hydrogen-depleted molecule, electronegativity, mass, and neighbors of carbon atoms are the main independent factors contributing to the skin-irritant effect of the thietanes.

Graphical Abstract

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Draize JH, Woodard G, Calvery HO (1944) J Pharmacol Exp Ther 82:77

    Google Scholar 

  2. Draize JH (1959) Dermal toxicity. Appraisal of the safety of chemicals in foods, drugs, and cosmetics. Association of foods and drugs officials of the United States. Littleton, CO, pp 46–59

    Google Scholar 

  3. Hill DL (1972) The biochemistry and physiology of Tetrahymena, 1st edn. Academic Press, New York

    Google Scholar 

  4. Riahi S, Pourbasheer E, Dinarvand R, Ganjali MR, Norouzi P (2008) Chem Biol Drug Des 72:575

    Article  CAS  Google Scholar 

  5. Riahi S, Pourbasheer E, Ganjali MR, Norouzi P (2008) Chem Biol Drug Des 72:205

    Article  CAS  Google Scholar 

  6. Riahi S, Ganjali MR, Pourbasheer E, Norouzi P (2008) Chromatographia 6:917

    Article  Google Scholar 

  7. Riahi S, Pourbasheer E, Ganjali MR, Norouzi P (2009) J Hazard Mater 166:853

    Article  CAS  Google Scholar 

  8. Khadikar PV, Phadnis A, Shrivastava A (2002) Bioorg Med Chem 10:1181

    Article  CAS  Google Scholar 

  9. Agrawal VK, Khadikar PV (2001) Bioorg Med Chem 9:3035

    Article  CAS  Google Scholar 

  10. Bratt MD (1996) Toxicol In Vitro 10:247

    Article  Google Scholar 

  11. Golla S, Madihally S, Robinson RL Jr, Gasem KAM (2009) Toxicol In Vitro 23:176

    Article  CAS  Google Scholar 

  12. Hayashi M, Nakamura Y, Higashi K, Kato H, Kishida F, Kaneko H (1999) Toxicol In Vitro 13:915

    Article  CAS  Google Scholar 

  13. Kodithala K, Hopfinger AJ, Thompson ED, Robinson MK (2002) Toxicol Sci 66:336

    Article  CAS  Google Scholar 

  14. Zhang JX, Sun LX, Zhang ZB, Wang ZW, Chen Y, Wang R (2002) J Chem Ecol 28:1287

    Article  CAS  Google Scholar 

  15. Shih M, David LL, Lampi KJ, Ma H, Fukiage C, Azuma M, Shearer TR (2001) Curr Eye Res 22:458

    Article  CAS  Google Scholar 

  16. Hansch C, Taylor J, Sammes P (1990) Comprehensive medicinal chemistry: the rational design, mechanistic study and therapeutic application of chemical compounds. vol 6. Pergamon, New York, pp 1–19

  17. Tropsha A, Gramatica P, Gombar VK (2003) QSAR Comb Sci 22:69

    Article  CAS  Google Scholar 

  18. Todeschini R, Consonni V (2000) Handbook of molecular descriptors. Wiley, Weinheim

    Book  Google Scholar 

  19. Raymond SA, Steffensen SC, Gudino LD, Strichartz GR (1989) Anesth Analg 68:563

    Article  CAS  Google Scholar 

  20. Stepanchikova AV, Lagunin AA, Filimonov DA, Poroikov VV (2003) Current Med Chem 10:225

    CAS  Google Scholar 

  21. Todeschini R, Consonni V, Pavana M (2002) Dragon, Software version 2.1. http://www.disat.unimib.it/chm/

  22. HyperChem Release 7. HyperCube, Inc, Alberta, Canada; http://www.hyper.com

  23. Hunger J, Huttner G (1999) J Comput Chem 20:455

    Article  CAS  Google Scholar 

  24. Ahmad S, Gromiha MM (2003) J Comput Chem 24:1313

    Article  CAS  Google Scholar 

  25. Waller CL, Bradley MP (1999) J Chem Inf Comput Sci 39:345

    CAS  Google Scholar 

  26. Aires-de-Sousa J, Hemmer MC, Gasteiger J (2002) Anal Chem 74:80

    Article  CAS  Google Scholar 

  27. The Mathworks Inc (2002) Genetic algorithm and direct search toolbox users guide, Massachusetts

  28. Gramatica P (2007) QSAR Comb Sci 26:694

    Article  CAS  Google Scholar 

  29. Atkinson AC (1985) Plots, transformations and regression: an introduction to graphical methods of diagnostic regression analysis. Clarendon Press, Oxford

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Imam Hossein University, Tehran, Iran

    Issa Kakoie Dinaki & Morteza Zarrineh

Authors
  1. Issa Kakoie Dinaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Morteza Zarrineh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Morteza Zarrineh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kakoie Dinaki, I., Zarrineh, M. A quantitative structure–activity relationship study of the skin-irritant effect of thietanes. Monatsh Chem 141, 1321–1328 (2010). https://doi.org/10.1007/s00706-010-0405-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00706-010-0405-2

Keywords

Search

Navigation