Document Type: Original Research Article

Author

Department of Chemistry, Shahrood Branch, Islamic Azad University, shahrood, Iran

Abstract

In this paper, the quantitative structure activity-relationship (QSAR) of the CCR2b receptor inhibitors was scrutinized. Firstly, the molecular descriptors were calculated using the Dragon package. Then, the stepwise multiple linear regressions (SW-MLR) and the genetic algorithm multiple linear regressions (GA-MLR) variable selection methods were subsequently employed to select and implement the prominent descriptors having the most significant contributions to the activities of the molecules. A combined data set including numerical values of inhibition activity data (IC50) of 103 CCR2b receptor derivatives was adopted for our simulations. This study revealed that both SW-MLR and GA-MLR methods consisted of six molecular descriptors. The adopted descriptors belong to topological, charge, RDF and atom-centered fragments classes. A comparison of results by the two methodologies indicated the superiority of GA-MLR over the SW-MLR method. The authenticity of the proposed model (GA-MLR) was further confirmed using the cross-validation, validation through an external test set and Y-randomization.

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[1] J. Saunders, C.M. Tarby, Drug Discov. Today, 1999, 4, 80-92.

[2] M. Navab, S.Y. Hama, T.B. Nguyen, A.M. Fogelman, Coron. Artery Dis., 1994, 5, 198-204.

[3] J.H. Gong, L.G. Ratkay, J.D. Waterfield, I. Clarc-Lewis, J. Exp. Med., 1977, 186, 131-137.

[4] C.M. Lloyd, A.W. Minto, M.E. Dorf, A. Proudfoot, T.N.C. Wells, D.J. Salant, J.C. Gutierrz-Ramos, J. Exp. Med., 1977, 185, 1371-1380.

[5] K.J. Kennedy, R.M. Strieter, S.L. Kunkel, N.W. Lukacs, W.J. Karpus, J. Neuroimmunol., 1998, 92, 98-108.

[6] V. Consonni, R. Todeschini, M. Pavan, J. Chem. Inf. Comput. Sci., 2002, 42, 682-692.

[7] K. Benyounis, A. Olabi, Adv. Eng. Softw., 2008, 39, 483-496.

[8] M. Mohammadhosseini, Asian J. Chem., 2012, 24, 3814-3820.

[9] M. Mohammadhosseini, O. Deeb, A. Alavi-Gharabagh, M. Nekoei, Anal. Chem. Lett., 2012, 2, 80-102.

[10] M. Mohammadhosseini, M. Nekoei, Asian J. Chem., 2013, 25, 349-352.

[11] M. Mohammadhosseini, H.A. Zamani, H. Akhlaghi, M. Nekoei, J. Essent. Oil-Bear. Plants, 2011, 14, 559-573.

[12] E.P. Box, N.R. Draper, Empirical Model Building and Response Surfaces, Wiley and Sons, EUA, 1987.

[13] M. Nekoei, M. Mohammadhosseini, A. Alavi-Gharahbagh, Anal. Bioanal. Electrochem., 2009, 1, 159-168.

[14] M. Mohammadhosseini, Anal. Chem. Lett., 2013, 3, 226-248.

[15] M. Mohammadhosseini, J. Chem. Health Risks, 2014, 4, 75-95.

[16] M. Imai, T. Shiota, K.-i. Kataoka, C.M. Tarby, W.J. Moree, T. Tsutsumi, M. Sudo, M.M. Ramirez-Weinhouse, D. Comer, C.-M. Sun, Bioorg. Med. Chem. Lett., 2004, 14, 5407-5411.

[17] W.J. Moree, K.-i. Kataoka, M.M. Ramirez-Weinhouse, T. Shiota, M. Imai, M. Sudo, T. Tsutsumi, N. Endo, Y. Muroga, T. Hada, Bioorg. Med. Chem. Lett., 2004, 14, 5413-5416.

[18] W.J. Moree, K.-i. Kataoka, M.M. Ramirez-Weinhouse, T. Shiota, M. Imai, T. Tsutsumi, M. Sudo, N. Endo, Y. Muroga, T. Hada, Bioorg. Med. Chem. Lett., 2008, 18, 1869-1873.

[19] D. Goldberg, Genetic Algorithms & Engineering Optimization, Wiley, New York, 1989.

[20] M. Nekoei, M. Salimi, M. Dolatabadi, M. Mohammadhosseini, Monatsh. Chem., 2011, 142, 943-948.

[21] M. Nekoei, N. Goudarzi, S. Nekoei, M. Mohammadhosseini, Anal. Chem. Lett., 2014, 4, 14-28.

[22] M. Nekoei, M. Mohammadhosseini, E. Pourbasheer, Med. Chem. Res., 2015, 24, 3037-3046.

[23] M. Nekoei, M. Salimi, M. Dolatabadi, M. Mohammadhosseini, J. Serb. Chem. Soc., 2011, 76, 1117-1127.

[24] G. Mitsuo, C. Runwei, Genetic Algorithms & Engineering Optimization, John Wiley & Sons, 2002.

[25] S. Ahmad, M.M. Gromiha, J. Comput. Chem., 2003, 24, 1313-1320.

[26] J. Hunger, G. Huttner, J. Comput. Chem., 1999, 20, 455-471.

[27] C.L. Waller, M.P. Bradley, J. Chem. Inf. Comput. Sci., 1999, 39, 345-355.

[28] M. Shahlaei, A. Fassihi, L. Saghaie, E. Arkan, A. Pourhossein, Daru, 2011, 19, 376.

[29] R. Wehrens, H. Putter, L.M. Buydens, Chemometr. Intell. Lab. Syst., 2000, 54, 35-52.

[30] P. Gramatica, QSAR Comb Sci., 2007, 26, 694.

[31] S. Riahi, M.R. Ganjali, E. Pourbasheer, P. Norouzi, Chromatographia, 2008, 67, 917-922.

[32] S. Riahi, E. Pourbasheer, M.R. Ganjali, P. Norouzi, Chem. Biol. Drug Des., 2009, 73, 558-571.

[33] R. Todeschini, V. Consonni, Handbook of Molecular Descriptors, John Wiley & Sons2008.

[34] D. Bonchev, Information-Theoretic Indices for Characterization of Chemical Structures, RSP/Willey,, Chichester, UK, 1983.

[35] D.L. Massart, B.G.M. Vandeginste, L.M.C. Buydens, S.D.E. Jong, Leui, P. J., J. Smeyers-Verbeke, Hand Book of Chemometrics and Qualimetrics: Part A., Elsevier1977.