QSAR modeling for lipid peroxidation inhibition potential of flavonoids using topological and structural parameters

Supratim Ray 1 , Chandana Sengupta 1 ,  and Kunal Roy 1
  • 1 Drug Theoretics and Cheminformatics Lab, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India

Abstract

In the present study, Quantitative Structure-Activity Relationship (QSAR) modeling has been carried out for lipid peroxidation (LPO)-inhibition potential of a set of 27 flavonoids, using structural and topological parameters. For the development of models, three methods were used: (1) stepwise regression, (2) factor analysis followed by multiple linear regressions (FA-MLR) and (3) partial least squares (PLS) analysis. The best equation was obtained from stepwise regression analysis (Q2 = 0.626) considering the leave-oneout prediction statistics.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • [1] J. M. C. Gutteridge, B. Halliwell, Antioxidants in Nutrition, Health and Disease, (Oxford University Press, Oxford, 1994) 12

  • [2] M. Parola, G. Belloma, G. Robino, G. Barrera, M.U. Dianzani, Antioxid. Redox Signal, 1, 255 (1999) http://dx.doi.org/10.1089/ars.1999.1.3-255

  • [3] J. L. Marx, Science, 107, 526 (1987)

  • [4] T. F. Slater, B. C. Sawyar, Biochem. J., 123, 805 (1971)

  • [5] B. Halliwell, Drugs, 42, 569 (1990) http://dx.doi.org/10.2165/00003495-199142040-00003

  • [6] X. Luo, Y. Evrovsky, D. Cole, J. Trines, L. N. Benson, D.C. Lehotay, Biochim. Biophys. Acta, 1360, 45 (1997)

  • [7] I. Durak, H. Perk, M. Kavutch, O. Combolat, O. Akyal and Y. Beduk, Free Radical Biol. Med., 16, 825 (1994) http://dx.doi.org/10.1016/0891-5849(94)90199-6

  • [8] A. K. Ratty, J. Sunamoto, N. P. Das, Biochem. Pharmacol., 37, 989 (1983) http://dx.doi.org/10.1016/0006-2952(88)90499-6

  • [9] P. C. H. Haollman, I. C. W. Arts, J. Sci. Food Agric., 80, 1081 (2000) http://dx.doi.org/10.1002/(SICI)1097-0010(20000515)80:7<1081::AID-JSFA566>3.0.CO;2-G

  • [10] S. A. Aherne, N. M. O’Brien, Nutrition, 18, 75 (2002) http://dx.doi.org/10.1016/S0899-9007(01)00695-5

  • [11] O. P. Agarwal, Agents Actions, 12, 298 (1982) http://dx.doi.org/10.1007/BF01965393

  • [12] M. K. Church, Drugs Today, 14, 281 (1978)

  • [13] T. Ozawa, Physiol. Rev., 77, 425 (1997)

  • [14] S. Luangaram, U. Kukongviriyapan, P. Pakdeechote, V. Kukongviriyapan, P. Pannangpetch, Food Chem. Toxicol., 45, 448 (2007) http://dx.doi.org/10.1016/j.fct.2006.09.008

  • [15] S. Chaudhuri, A. Banerjee, K. Basu, B. Sengupta, P.K. Sengupta, Int. J. Biol. Macromol., 41, 42 (2007) http://dx.doi.org/10.1016/j.ijbiomac.2006.12.003

  • [16] A. L. Miller, Alt. Med. Rev., 1, 103 (1996)

  • [17] N. C. Cook, S. Samman, J. Nutr. Biochem., 7, 66 (1996) http://dx.doi.org/10.1016/0955-2863(95)00168-9

  • [18] E. Middleton, Int. J. Pharmacog., 34, 344 (1996)

  • [19] O. Farkas, J. Jakus, K. Heberger, Molecules, 9, 1079 (2004) http://dx.doi.org/10.3390/91201079

  • [20] A. I. Khlebnikov, I. A. Schepetkin, N. G. Domina, L. N. Kirpotina, M. T. Quinn, Bioorg. Med. Chem., 15, 1749 (2007) http://dx.doi.org/10.1016/j.bmc.2006.11.037

  • [21] A. Thakur, S. Vishwakarma, M. Thakur, Bioorg. Med. Chem., 12, 1209 (2004) http://dx.doi.org/10.1016/j.bmc.2003.11.024

  • [22] R. Badhan, J. Penny, Eur. J. Med. Chem., 41, 285 (2006) http://dx.doi.org/10.1016/j.ejmech.2005.11.012

  • [23] A. Karawajczyk, V. Drgan, N. Medic, G. Oboh, S. Passamonti, M. Novic, Biochem. Pharmacol., 73, 308 (2007) http://dx.doi.org/10.1016/j.bcp.2006.09.024

  • [24] J. Lameira, C. N. Alves, V. Moliner, E. Silla, Eur J. Med. Chem., 41, 616 (2006) http://dx.doi.org/10.1016/j.ejmech.2006.01.008

  • [25] S. Zhang, X. Yang, R. A. Coburn, M. E. Morris, Biochem. Pharmacol., 70, 627 (2005). http://dx.doi.org/10.1016/j.bcp.2005.05.017

  • [26] C. N. Alves, J. C. Pinheiro, A. J. Camargo, M. M. C. Ferreira, R. A. F. Romero, A. B. F. da Silva, J. Mol. Struct. (Theochem), 541, 81 (2001) http://dx.doi.org/10.1016/S0166-1280(00)00755-7

  • [27] D. Amic, D.D. Amic, D. Beslo, N. Trinajstic, Croat. Chem. Acta, 76, 55 (2003)

  • [28] B. F. Rasulev, N. D. Abdullaev, V. N. Syrov, J. Leszczynski, QSAR Comb. Sci., 24, 1056 (2005) http://dx.doi.org/10.1002/qsar.200430013

  • [29] C. Silipo, A. Vittoria, In: C. Hansch, P. G. Sammes, J. B. Taylor (Eds.), Comprehensive Medicinal Chemistry: The Rational Design, Mechanistic Study & Theoretical Application of Chemical Compounds, Quantitative Drug Design, Vol. 4 (Pergamon Press, Oxford, 1990) 183

  • [30] A. T. Balaban, Chem. Phys. Lett., 89, 399 (1982) http://dx.doi.org/10.1016/0009-2614(82)80009-2

  • [31] L.B. Kier, Quant. Struct.-Act. Relat., 4, 109 (1985) http://dx.doi.org/10.1002/qsar.19850040303

  • [32] M. Randic, J. Am. Chem. Soc., 97, 6609 (1975) http://dx.doi.org/10.1021/ja00856a001

  • [33] L. B. Kier, L. H. Hall, J. Chem. Inf. Comput. Sci., 40, 784 (2000) http://dx.doi.org/10.1021/ci000326r

  • [34] H. Wiener, J. Am. Chem. Soc., 69, 17 (1947) http://dx.doi.org/10.1021/ja01193a005

  • [35] L. Gutman, B. Ruscic, N. Trinajstic, C. F. Wilcox, J. Chem. Phys., 62, 3399 (1975) http://dx.doi.org/10.1063/1.430994

  • [36] L. B. Kier, L. H. Hall, Molecular Connectivity in Chemistry and Drug Research, (Academic Press, New York, 1976)

  • [37] L. B. Kier, In: D. H. Rouvray (Ed.), Computational Graph Theory (Nova Science Publisher, New York, 1990) 152

  • [38] L. H. Hall, B. Mohney, L.B. Kier, Quant. Struct.-Act. Relat., 10, 43 (1991) http://dx.doi.org/10.1002/qsar.19910100108

  • [39] L. B. Kier, L.H. Hall, Pharm. Res., 7, 801 (1990) http://dx.doi.org/10.1023/A:1015952613760

  • [40] L. H. Hall, B. Mohney, L. B. Kier, Quant. Struct.-Act. Relat., 12, 44 (1993) http://dx.doi.org/10.1002/qsar.19930120107

  • [41] K. Roy, A.U. De, C. Sengupta, Indian J. Chem., 38B, 942 (1999)

  • [42] A. Saha, K. Roy, K. De, C. Sengupta, J. Indian Chem. Soc., 78, 92 (2001)

  • [43] K. Roy, D. K. Pal, C. Sengupta, Drug Des. Discov., 17, 207 (2001)

  • [44] K. Roy, A. U. De, C. Sengupta, Drug Des. Discov., 18, 23 (2002) http://dx.doi.org/10.1080/10559610213503

  • [45] K. Roy, S. Chakraborty, A. Saha, Bioorg. Med. Chem. Lett., 13, 3753 (2003) http://dx.doi.org/10.1016/j.bmcl.2003.07.002

  • [46] K. Roy, J. T. Leonard, Bioorg. Med. Chem., 12, 745 (2004) http://dx.doi.org/10.1016/j.bmc.2003.11.009

  • [47] S. Chakraborty, C. Sengupta, K. Roy, Bioorg. Med. Chem. Lett., 14, 4665 (2004) http://dx.doi.org/10.1016/j.bmcl.2004.06.095

  • [48] C. Sengupta, J. T. Leonard, K. Roy, Bioorg. Med. Chem. Lett., 14, 3435 (2004) http://dx.doi.org/10.1016/j.bmcl.2004.04.073

  • [49] S. Ray, C. Sengupta, K. Roy, Cent. Eur. J. Chem., 5, 1094 (2007) http://dx.doi.org/10.2478/s11532-007-0047-3

  • [50] R. B. Darlington, Regression and Linear Models (McGraw Hill, New York, 1990)

  • [51] R. Franke, Theoretical Drug Design Methods (Elsevier, Amsterdam, 1984)

  • [52] R. Franke, A. Gruska, In: H. van de Waterbeemd (Ed), Chemometric Methods in Molecular Design (VCH, Weinheim, 1995) 113 http://dx.doi.org/10.1002/9783527615452.ch4

  • [53] S. Wold, In: H. vande Waterbeemd (Ed); Chemometric Methods in Molecular Design (VCH, Weinheim, 1995) 195

  • [54] Y. Fan, L. M. Shi, K.W. Kohn, Y. Pommier, J.N. Weinstein, J. Med. Chem., 44, 3254 (2001) http://dx.doi.org/10.1021/jm0005151

  • [55] The GW-BASIC program ELECTRO1 was developed by Kunal Roy and standardized on known data sets

  • [56] Cerius2 version 4.8 is a product of Accelrys, Inc., San Diego, USA, http://www.accelrys.com/cerius2

  • [57] SPSS is statistical software of SPSS Inc., IL, USA

  • [58] MINITAB is statistical software of Minitab Inc, USA, http://www.minitab.com

  • [59] G. W. Snedecor, W.G. Cochran, Statistical Methods (Oxford & IBH Publishing Co. Pvt. Ltd, New Delhi, 1967)

  • [60] S. Wold, L. Eriksson, In: H. van de Waterbeemd (Ed), Chemometric Methods in Molecular Design (VCH, Weinheim, 1995) 312

  • [61] A. K. Debnath, In: A. K. Ghose, V. N. Viswanadhan (Eds), Combinatorial Library Design and Evaluation: Principles, Software, Tools and Application in Drug Discovery (Marcel Dekker Inc, NewYork, 2001) 73

  • [62] J. D. Walker, J. Jaworska, M. H. Comber, T. W. Schultz, J. C. Dearden, Environ. Toxicol. Chem., 22, 1653 (2003) http://dx.doi.org/10.1897/01-627

OPEN ACCESS

Journal + Issues

Open Chemistry is a peer-reviewed, open access journal that publishes original research, reviews and short communications in the fields of chemistry in an ongoing way. Our central goal is to provide a hub for researchers working across all subjects to present their discoveries, and to be a forum for the discussion of the important issues in the field.

Search