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Chemometric Modeling to Predict Aquatic Toxicity of Benzene Derivatives Using Stepwise-Multi Linear Regression and Partial Least Square
Corresponding Author(s) : Maryam Bordbar
Asian Journal of Chemistry,
Vol. 25 No. 1 (2013): Vol 25 Issue 1
Abstract
The aquatic toxicity of 392 benzene derivatives have been subjected to quantitative structure-activity relationship studies. Optimization of 3D structures of the molecules carried out by HyperChem using AM1 model. The molecular descriptors; constitutional, topological, molecular walk counts, aromaticity indices, geometrical, WHIM, functional group, empirical and properties were obtained by Dragon software. The models were constructed using 309 molecules as training set and predictive ability tested using 78 compounds. Modeling of log (1/IGC50) of these compounds as a function of the theoretically derived descriptors was established by multiple linear regression (MLR) technique. This linear modeling method indicates the importance of different topological and electronic descriptors on the aquatic toxicity [log (1/IGC50)]. The obtained model (stepwise MLR-PLS) was chosen based on highest external predictive R2 value (0.81) and lowest RMSEP (2.41) values. It is observed that the Moriguchi octanol/water partition coefficient (log P) descriptor has great effect on the aquatic toxicity, which confirms its importance in mechanism of aquatic toxicity action of benzene derivatives.
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References
A. Worth, A. Bassan, J. De Bruijn, A. Saliner, T. Netzeva, G. Patlewicz, M. Pavan, I. Tsakovska and S. Eisenreich, SAR QSAR Environ. Res., 18, 111 (2007).
C. Hansch, P.P. Maloney, T. Fujita and R.M. Muir, Nature, 194, 178 (1962).
R. Todeschini and V. Consonni, Handbook of Molecular Descriptors, Weinheim: Wiley-VCH (2000).
M. Karelson, Molecular Descriptors in QSAR/QSPR, Wiley-Interscience (2000); B. Hemmateenejad, M. Safarpour and F. Taghavi, J. Mol. Struct. (Theochem.), 635, 183 (2003); I. Moriguchi, S. Hirono, Q. Liu, I. Nakagome and Y. Matsushita, Chem. Pharm. Bull. (Tokyo), 40, 127 (1992).
W. Tong, H. Hong, Q. Xie, L. Shi, H. Fang and R. Perkins, Curr. Comput. Aided Drug. Des., 1, 195 (2005); L. He and P. Jurs, J. Mol. Graphics Model., 23, 503 (2005); T. Ghafourian and M. Cronin, SAR QSAR Environ. Res., 16, 171 (2005); A. Tropsha, P. Gramatica and V. Gombar, QSAR Comb. Sci., 22, 69 (2003); A. Golbraikh and A. Tropsha, J. Mol. Graphics Model., 20, 269 (2002).
S. Wold and L. Eriksson, Chemometric Methods in Molecular Design, VCH, Weinheim, Vol. 195 (1995).
S.D. Brown, S.T. Sum, F. Despagne and B.K. Lavine, Ana. Ch., 68, 21 (1996); K. Roy and J. Leonard, Bioorg. Med. Chem., 13, 2967 (2005).
T. Schultz, T. Netzeva, in Predicting Chemical Toxicity and Fate, p. 265 (2004).
S. Bradbury, C. Russom, G. Ankley, T. Schultz and J. Walker, Environ. Toxicol. Chem., 22, 1789 (2009).
R. Johnson and D. Wichern, Applied Multivariate Statistical Analysis, Prentice Hall Englewood Cliffs, NJ, (1998); J. Mc Farland and D. Gans, Chapter Cluster Significance Analysis, VCH, Weinheim, 295 (1995).
P. Broto, G. Moreau and C. Vandycke, Eur. J. Med. Chem., 19, 61 (1984); J. Gálvez, R. García, M. Salabert and R. Soler, J. Chem. Inf. Comput. Sci., 34, 520 (1994); L. Kier and L. Hall, Molecular Connectivity in Structure-Activity Analysis, Wiley, New York (1986); E. Konstantinova, J. Chem. Inf. Comput. Sci., 36, 54 (1996); G. Ruecker and C. Ruecker, J. Chem. Inf. Comput. Sci., 33, 683 (1993).
M. Dewar, E. Zoebisch, E. Healy and J. Stewart, J. Am. Chem. Soc., 107, 3902 (1985).
J. Xu and A. Hagler, Molecules, 7, 566 (2002).
R. Leardi and A. Lupiáñez González, Chemometrics Intell. Lab. Syst., 41, 195 (1998).
P. Geladi and B. Kowalski, Anal. Chim. Acta, 185, 1 (1986).
R. Leardi, R. Boggia and M. Terrile, J. Chemometrics, 6, 267 (2005).
D. Goldberg, Genetic Algorithms in Search, Optimization and Machine Learning Addision Wesley Longman Inc, MA, USA (1989).
R. Yu, Introduction to Chemometrics, Changsha, Hunan Education House, Vol. 67 (1991).
B. Dayal and J. MacGregor, J. Chemometrics, 11, 73 (1998).
J. Castillo-Garit, Y. Marrero-Ponce, J. Escobar, F. Torrens and R. Rotondo, Chemosphere, 73, 415 (2008).