A QSAR Study of Radical Scavenging Antioxidant Activity of a Series of Flavonoids Using DFT Based Quantum Chemical Descriptors--the Importance of Group Frontier Electron Density

Overview

Journal J Mol Model

Publisher Springer

Specialty Molecular Biology

Date 2011 Nov 15

PMID 22080306

Citations 19

Authors

Ananda Sarkar

Tapas Ranjan Middya

Atish Dipnakar Jana

Affiliations

Soon will be listed here.

Abstract

In a pursuit of electronic level understanding of the antioxidant activity of a series of flavonoids, quantitative structure-activity relationship (QSAR) studies have been carried out using density functional theory (DFT) based quantum chemical descriptors. The best QSAR model have been selected for which the computed square correlation coefficient r(2) = 0.937 and cross-validated squared correlation coefficient q(2) =0.916. The QSAR model indicates that hardness (η), group electrophilic frontier electron density (F(E)(A)) and group philicity (ω(B)(+)) of individual molecules are responsible for in vitro biological activity. To the best our knowledge, the group electrophilic frontier electron density (F(E)(A)) has been used for the first time to explain the radical scavenging activity (RSA) of flavonoids. The excellent correlation between the RSA and the above mentioned DFT based descriptors lead us to predict new antioxidants having very good antioxidant activity.

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References

Cao G, Sofic E, Prior R . Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships. Free Radic Biol Med. 1997; 22(5):749-60. DOI: 10.1016/s0891-5849(96)00351-6. View

Thomas B, Compton D, Martin B, Semus S . Modeling the cannabinoid receptor: a three-dimensional quantitative structure-activity analysis. Mol Pharmacol. 1991; 40(5):656-65. View

MIDDLETON Jr E . Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol. 1998; 439:175-82. DOI: 10.1007/978-1-4615-5335-9_13. View

Hawkins D, Basak S, Mills D . Assessing model fit by cross-validation. J Chem Inf Comput Sci. 2003; 43(2):579-86. DOI: 10.1021/ci025626i. View

Block G . The data support a role for antioxidants in reducing cancer risk. Nutr Rev. 1992; 50(7):207-13. DOI: 10.1111/j.1753-4887.1992.tb01329.x. View

Yang W, Mortier W . The use of global and local molecular parameters for the analysis of the gas-phase basicity of amines. J Am Chem Soc. 2011; 108(19):5708-11. DOI: 10.1021/ja00279a008. View

Simic M, Bergtold D, Karam L . Generation of oxy radicals in biosystems. Mutat Res. 1989; 214(1):3-12. DOI: 10.1016/0027-5107(89)90192-9. View

Taubert D, Breitenbach T, Lazar A, Censarek P, Harlfinger S, Berkels R . Reaction rate constants of superoxide scavenging by plant antioxidants. Free Radic Biol Med. 2003; 35(12):1599-607. DOI: 10.1016/j.freeradbiomed.2003.09.005. View

Karelson M, Lobanov V, Katritzky A . Quantum-Chemical Descriptors in QSAR/QSPR Studies. Chem Rev. 1996; 96(3):1027-1044. DOI: 10.1021/cr950202r. View

10.

Zhou B, Miao Q, Yang L, Liu Z . Antioxidative effects of flavonols and their glycosides against the free-radical-induced peroxidation of linoleic acid in solution and in micelles. Chemistry. 2004; 11(2):680-91. DOI: 10.1002/chem.200400391. View

11.

Golbraikh A, Shen M, Xiao Z, Xiao Y, Lee K, Tropsha A . Rational selection of training and test sets for the development of validated QSAR models. J Comput Aided Mol Des. 2003; 17(2-4):241-53. DOI: 10.1023/a:1025386326946. View

12.

Pietta P . Flavonoids as antioxidants. J Nat Prod. 2000; 63(7):1035-42. DOI: 10.1021/np9904509. View

13.

Hawkins D . The problem of overfitting. J Chem Inf Comput Sci. 2004; 44(1):1-12. DOI: 10.1021/ci0342472. View

14.

Gabor M . Anti-inflammatory and anti-allergic properties of flavonoids. Prog Clin Biol Res. 1986; 213:471-80. View

15.

Zhang L, Wan J, Yang G . A DFT-based QSARs study of protoporphyrinogen oxidase inhibitors: phenyl triazolinones. Bioorg Med Chem. 2004; 12(23):6183-91. DOI: 10.1016/j.bmc.2004.08.046. View

16.

Zhang H, Sun Y, Wang X . Substituent effects on O--H bond dissociation enthalpies and ionization potentials of catechols: a DFT study and its implications in the rational design of phenolic antioxidants and elucidation of structure-activity relationships for flavonoid.... Chemistry. 2003; 9(2):502-8. DOI: 10.1002/chem.200390052. View

17.

Aherne S, OBrien N . Dietary flavonols: chemistry, food content, and metabolism. Nutrition. 2002; 18(1):75-81. DOI: 10.1016/s0899-9007(01)00695-5. View

18.

Di Carlo G, Mascolo N, Izzo A, Capasso F . Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sci. 1999; 65(4):337-53. DOI: 10.1016/s0024-3205(99)00120-4. View

19.

Bors W, Heller W, Michel C, Saran M . Flavonoids as antioxidants: determination of radical-scavenging efficiencies. Methods Enzymol. 1990; 186:343-55. DOI: 10.1016/0076-6879(90)86128-i. View

20.

Wan J, Zhang L, Yang G, Zhan C . Quantitative structure-activity relationship for cyclic imide derivatives of protoporphyrinogen oxidase inhibitors: a study of quantum chemical descriptors from density functional theory. J Chem Inf Comput Sci. 2004; 44(6):2099-105. DOI: 10.1021/ci049793p. View