[en] A quantitative structure-activity relationship (QSAR) study of the 2,2-diphenyl-l-picrylhydrazyl (DPPH‚) radical scavenging ability of 1373 chemical compounds, using DRAGON molecular descriptors (MD) and the neural network technique, a technique based on the multilayer multilayer perceptron (MLP), was developed. The built model demonstrated a satisfactory performance for the training `R2 “ 0.713 ̆ and test set `Q2ext “ 0.654 ̆, respectively. To gain greater insight on the relevance of the MD contained in the MLP model, sensitivity and principal component analyses were performed. Moreover, structural and mechanistic interpretation was carried out to comprehend the relationship of the variables in the model with the modeled property. The constructed MLP model was employed to predict the radical scavenging ability for a group of coumarin-type compounds. Finally, in order to validate the model’s predictions, an in vitro assay for one of the compounds (4-hydroxycoumarin) was performed, showing a satisfactory proximity between the experimental and predicted pIC50 values.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Goya-Jorge, Elizabeth ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Gestion de la qualité dans la chaîne alimentaire
Rayar, Anita Maria; Conservatoire National des Arts et Métiers > PhD
Barigye, Stephen J; ProtoQSAR SL > PhD
Jorge-Rodríguez, María Elisa; Universidad Central "Marta Abreu" de las Villas > Department of Pharmacy > Professor
Veitía, Maité Sylla-Iyarreta; Conservatoire National des Arts et Métiers > Equipe de Chimie Moléculaire du Laboratoire Génomique, Bioinformatique et Chimie Moléculaire (EA 7528) > Professor
Language :
English
Title :
Development of an in Silico Model of DPPH‚ Free Radical Scavenging Capacity: Prediction of Antioxidant Activity of Coumarin Type Compounds
Publication date :
07 June 2016
Journal title :
International Journal of Molecular Sciences
ISSN :
1661-6596
eISSN :
1422-0067
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Special issue title :
Big Data Analysis and QSAR/QSPR Research in Chemistry, Bio-Medical, and Network Sciences
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Bibliography
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 2007, 39, 44-84. [CrossRef] [PubMed]
Magalhaes, L.M.; Segundo, M.A.; Reis, S.; Lima, J.L.F.C. Methodological aspects about in vitro evaluation of antioxidant properties. Anal. Chim. Acta 2008, 613, 1-19. [CrossRef] [PubMed]
Scalzo, J.; Mezzetti, B.; Battino, M. Total antioxidant capacity evaluation: Critical steps for assaying berry antioxidant features. BioFactors 2005, 23, 221-227. [CrossRef] [PubMed]
Niki, E. Assessment of Antioxidant Capacity in vitro and in vivo. Free Rad. Biol. Med. 2010, 49, 503-515. [CrossRef] [PubMed]
Gunars, T.; Grzegorz, B. Determination of antiradical and antioxidant activity: Basic principles and new insights. Acta Biochim. Pol. 2010, 57, 139-142.
Kedare, S.; Singh, R. Genesis and development of DPPH method of antioxidant assay. J. Food Sci. Technol. 2011, 48, 412-422. [CrossRef] [PubMed]
Naceur, H.; Fischmeister, C.; Puerta, M.; Valerga, P. A rapid access to new coumarinyl chalcone and substituted chromeno[4,3-c]pyrazol-4(1H)-ones and their antibacterial and DPPH radical scavenging activities. Med. Chem. Res. 2011, 20, 522-530.
Puerta, M.; Naceur, H.; Valerga, P. Synthesis, structure, antimicrobial and antioxidant investigations of dicoumarol and related compounds. Eur. J. Med. Chem. 2008, 43, 2541-2548.
Fylaktakidou, K.; Hadjipavlou-Litina, D.; Litinas, K.; Nicolaides, D. Natural and synthetic coumarin derivatives with antiinflammatory/antioxidant activities. Curr. Pharm. 2004, 10, 3813-3833. [CrossRef]
Razo-Hernández, R.; Pineda-Urbina, K.; Velazco-Medel, M.; Villanueva-García, M.; Sumaya-Martínez, T.; Martínez-Martínez, F.; Gómez-Sandoval, Z. QSAR study of the DPPH‚ radical scavenging activity of coumarin derivatives and xanthine oxidase inhibition by molecular docking. Cent. Eur. J. Chem. 2014, 12, 1067-1080. [CrossRef]
Todeschini, R.; Consonni, V.; Gramatica, P. Chemometrics in QSAR. In Comprehensive Chemometrics Chemical and Biochemical Data Analysis; Brown, S., Tauler, R., Walczak, B., Eds.; Elsevier: Ámsterdam, The Netherlands, 2009; Volume 4, pp. 129-172.
Eriksson, L.; Jaworska, J.; Worth, A.; Cronin, M.; McDowell, R.; Gramatica, P. Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs. Environ. Health Perspect. 2003, 111, 1361-1375. [CrossRef] [PubMed]
Aoyama, T.; Suzuki, Y.; Ichikawa, H. Neural networks applied to structure-activity relationships. J. Med. Chem.1990, 33, 905-908. [CrossRef] [PubMed]
CORINA Classic (software); Molecular Networks GmbH: Erlangen, Germany, 2015. Available online: http://www.molecular-networks.com (accessed on 9 March 2015).
TALETE srl. MobyDigs (software), v1.0; Milano, Italy, 2004. Available online: http://www.talete.mi.it/mobydigs.htm (accessed on 2 June 2015).
StatSoft, Inc. STATISTICA (software), v8.0; Tulsa, OK, USA, 2007. Available online: http://www.statsoft.com (accessed on 7 June 2015).
Jeliazkova, N. Ambit Discovery (software), v0.04; Sofia, Bulgaria, 2005. Available online: http://www.ambit.acad.bg (accessed on 5 June 2015).
Tropsha, A. Best Practices for QSAR model development, validation, and exploitation. Mol. Inf. 2010, 29, 476-488. [CrossRef]
Todeschini, R.; Consonni, V. Handbook of Molecular Descriptors, 1st ed.; Wiley-VCH: Weinheim, Germany, 2000.
Wright, J.; Johnson, E.; DiLabio, G. Predicting the activity of phenolic antioxidants: Theoretical method, analysis of substituent effects, and application to major families of antioxidants. J. Am. Chem. Soc. 2001, 123, 1173-1183. [CrossRef] [PubMed]
Chen, Y.; Xiao, H.; Zheng, J.; Liang, G. Structure-thermodynamics-antioxidant activity relationships of selected natural phenolic acids and derivatives: An experimental and theoretical evaluation. PLoS ONE 2015, 10. [CrossRef] [PubMed]
Gupta, S.; Matthew, S.; Abreu, P.M.; Aires-de-Sousa, J. QSAR analysis of phenolic antioxidants using MOLMAP descriptors of local properties. Bioorg. Med. Chem. 2006, 14, 1199-1206. [CrossRef] [PubMed]
Jing, P.; Zhao, S.-J.; Jian, W.-J.; Qian, B.-J.; Dong, Y.; Pang, J. Quantitative studies on structure-DPPH scavenging activity relationships of food phenolic acids. Molecules 2012, 17, 12910-12924. [CrossRef] [PubMed]
Khlebnikov, A.I.; Schepetkin, I.A.; Domina, N.G.; Kirpotina, L.N.; Quinn, M.T. Improved quantitative structure-activity relationship models to predict antioxidant activity of flavonoids in chemical, enzymatic, and cellular systems. Bioorg. Med. Chem. 2007, 15, 1749-1770. [CrossRef] [PubMed]
Mitra, I.; Saha, A.; Roy, K. Quantitative structure-activity relationship modeling of antioxidant activities of hidroxybenzalacetones using quantum chemical, physicochemical and spatial descriptors. Chem. Biol. Drug. Des. 2009, 73, 526-536. [CrossRef] [PubMed]
Mitra, I.; Saha, A.; Roy, K. Chemometric modeling of free radical scavenging activiti of flavone derivatives. Eur. J. Med. Chem. 2010, 45, 5071-5079. [CrossRef] [PubMed]
Worachartcheewan, A.; Nantasenamat, C.; Isarankura-Na-Ayudhya, C.; Prachaiasittikul, S.; Prachaiasittikul, V. Predicting the free radical scavenging activity of curcumin derivatives. Chemometr. Intell. Lab. Syst. 2011, 109, 207-216. [CrossRef]
Yamagami, C.; Motohashi, N.; Emoto, T.; Hamasaki, A.; Tanahashi, T.; Nagakura, N.; Takeuchi, Y. Quantitative structure-activity relationship analyses of antioxidant and free radical scavenging activities for hydroxybenzalacetones. Bioorg. Med. Chem. Lett. 2004, 14, 5629-5633. [CrossRef] [PubMed]
Kadhum, A.; Al-Amiery, A.; Musa, A.; Mohamad, A. The antioxidant activity of new coumarin derivatives. Int. J. Mol. Sci. 2011, 12, 5747-5761. [CrossRef] [PubMed]
McInnes, C. Virtual screening strategies in drug discovery. Curr. Opin. Chem. Biol. 2007, 11, 494-502. [CrossRef] [PubMed]
Cseke, L.J.; Kirakosyan, A.; Kaufman, P.B.; Warber, S.; Duke, J.A.; Brielmann, H.L. Natural Products from Plants, 2nd ed.; CRC Press: New York, NY, USA, 2006.
ChemAxon Ltd. ChemAxon, 6.1.0 (software); Budapest, Hungary, 2013. Available online: http://www.chemaxon.com (accessed on 10 March 2015).
TALETE srl. DRAGON for Windows (Software for Molecular Descriptor Calculations), V 5.5; Milano, Italy, 2007. Available online: http://www.talete.mi.it/ (accessed on 15 March 2015).
Blois, M. Antioxidant determinations by the use of a stable free radical. Nature 1958, 181, 1199-1200.
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