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QSAR studies on estimation of monoamine oxidase-A inhibitory activity using topological descriptors

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Abstract

Quantitative structure activity relationship analysis has been performed with 32 synthetically derived analogues for their inhibitory effects on monoamine oxidase-A using two-dimensional topological descriptors. The topological descriptors used being total structure connectivity index, mean square distance index, mean wiener index, all-path wiener index, kier flexibility index, eccentric index and superpendentic index. The statistical analysis has shown that excellent results are obtained by using multiple linear regression method. The best model was selected based on the highest R 2 value (0.904). The results are discussed critically using variety of statistical parameters such as squared correlation coefficient (R 2), adjusted R 2, predicted residual sum of square (PRESS) and Pogliani’s quality factor (Q). The models were validated by using the method of leave-one and leave-many out cross-validation methods.

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References

  • Abdel-Hamid MK, Abdel-Hafez AA, El-Koussi NA, Mahfouz NM (2009) Quantitative structure-activity relationship (QSAR) studies on a series of 1,3,4-thiadiazole-2-thione derivatives as tumor-associated carbonic anhydrase. J Enzym Inhib Med Chem 24(3):722–729

    Article  CAS  Google Scholar 

  • Balaban AT (1983) Topological indices based on topological distances in molecular graphs. Pure Appl Chem 55:199–203

    Article  CAS  Google Scholar 

  • Chimenti F, Fioravanti R, Bolasco A, Manna F, Chimenti P, Secci D, Befani O, Turini P, Ortuso F, Alcaro S (2007) Synthesis and selective inhibitory activity against MAO of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives. J Med Chem 50:425–428

    Article  CAS  PubMed  Google Scholar 

  • Dietrich SW, Dreyer ND, Hansch C, Bentley DL (1980) Confidence interval estimators for parameters associated with quantitative structure-activity relationships. J Med Chem 23:1201–1205

    Article  CAS  PubMed  Google Scholar 

  • Dureja H, Kumar V, Gupta S, Madan AK (2007) Topochemical models for the prediction of lipophilicity of 1,3-disubstituted propan-2-one analogs. J Theor Comput Chem 6(3):435–448

    Article  CAS  Google Scholar 

  • Galvez J, Garcia R, Salabert MT, Soler R (1994) Charge indexes. New topological descriptors. J Chem Inf Comput Sci 34:520–525

    CAS  Google Scholar 

  • Gupta S, Singh M, Madan AK (1999) Superpendentic index: a novel topological descriptor for prediction of biological activity. J Chem Inf Comput Sci 39:272–277

    CAS  PubMed  Google Scholar 

  • Gute BD, Basak SC (1997) Predicting acute toxicity (LC50) of benzene derivatives using theoretical molecular descriptors: a hierarchical QSAR approach. SAR QSAR Environ Res 7:117–131

    Article  CAS  PubMed  Google Scholar 

  • Hadjipavloulitina D, Hansch C (1994) Quantitative structure−activity relationships of the benzodiazepines. A review and reevaluation. Chem Rev 94:1483–1505

    Article  CAS  Google Scholar 

  • Hansch C, Leo A, Mekapati SB, Kurup A (2004) QSAR and ADME. Bioorg Med Chem 12:3391–3400

    Article  CAS  PubMed  Google Scholar 

  • Jaiswal M, Khadikar V, Scozzafava A, Supuran CT (2004) Carbonic anhydrase inhibitors: the first QSAR study on inhibition of tumor-associated isoenzyme IX with aromatic and heterocyclic sulfonamides. Bioorg Med Chem Lett 14:3283–3290

    Article  CAS  PubMed  Google Scholar 

  • Kalgutkar AS, Dalvie DK, Castagnoli N Jr, Taylor TJ (2001) Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isozymes A and B: SAR studies on MAO substrates and inhibitors. Chem Res Toxicol 14:1139–1158

    Article  CAS  PubMed  Google Scholar 

  • Keir LB (1989) An index of molecular flexibility from kappa shape attribute. Quant Struct Act Relat 8:221–224

    Article  Google Scholar 

  • Kurup A, Mekapati SB, Garg R, Hansch C (2003) HIV-1 protease inhibitors: A comparative QSAR analysis. Curr Med Chem 10:1679–1688

    Article  CAS  PubMed  Google Scholar 

  • Lukvits I (1998) All-path version of the Wiener index. J Chem Inf Comp Sci 38:125–129

    Google Scholar 

  • Needham DE, Wei IC, Seybold PO (1998) Molecular mounting of the physical properties of the alkanes. J Chem Am Soc 110:4186–4194

    Article  Google Scholar 

  • Nikolic S, Trinajstic N, Baucic I (1998) Comparison between the vertex- and edge-connectivity indices for benzenoid hydrocarbons. J Chem Inf Comput Sci 38:42–46

    CAS  Google Scholar 

  • Nokolic S, Kovacevic G, Milicevic A, Trinajstic N (2003) The Zagreb indices 30 years after. Croat Chem Acta 76:113

    Google Scholar 

  • Randic M (1997) On characterization of chemical structure. J Chem Inf Comput Sci 37:672

    CAS  Google Scholar 

  • Randic M (1998) On characterization of molecular attributes. Acta Chim. Slov 45:239–252

    CAS  Google Scholar 

  • Regina GL, Silvestri R, Artico M, Lavecchia A, Novellino E, Befani O, Turini P, Agostinelli E (2007) New pyrrole inhibitors of monoamine oxidase: synthesis, biological evaluation, and structural determinantes of MAO-A and MAO-B selectivity. J Med Chem 50:922–931

    Article  PubMed  Google Scholar 

  • Roy K, Roy P (2008) Comparative QSAR studies of CYP1A2 inhibitor flavonoids using 2D and 3D descriptors. Chem Biol Drug Des 72:370–382

    Article  CAS  PubMed  Google Scholar 

  • Sardana S, Madan AK (2002) Predicting anticonvulsant activity of benzamides/benzylamines: computational approach using topological descriptors. J Comput Aided Mol Des 16:545–550

    Article  CAS  PubMed  Google Scholar 

  • Silvestri R, Regina GL, Martino GD, Artico M, Befani O, Palumbo M, Agostinelli E, Turini P (2003) Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B. J Med Chem 46:917–920

    Article  CAS  PubMed  Google Scholar 

  • Singh P, Kumar R, Sharma BK, Prabhakar YS (2009) Topological descriptors in modeling malonyl coenzyme A decarboxylase inhibitory activity: N-Alkyl-N-(1,1,1,3,3,3-hexafluoro-2-hydroxypropylphenyl)amide derivatives. J Enzym Inhib Med Chem 24(1):77–85

    Article  CAS  Google Scholar 

  • Skorobogatov VA, Dobrynin AA (1998) Metric analysis of graphs. MATCH Comm Math Comp Chem 23:105–151

    Google Scholar 

  • Talete Srl, DRAGON for windows (software for molecular descriptors calculations) version 5.5-2007- http://www.talete.mi.it/

  • Wiener H (1947) Structural determination of paraffin boiling points. J Am Chem Soc 69:17–20

    Article  CAS  PubMed  Google Scholar 

  • Wold S (1991) Validation of QSAR’s. Quant Struct Act Relat 10:191–193

    Article  CAS  Google Scholar 

  • Zhang S, Golbraikh A, Oloff S, Kohn H, Tropsha A (2006) A novel automated lazy learning QSAR (ALL-QSAR) approach: method development, applications, and virtual screening of chemical databases using validated ALL-QSAR models. J Chem Inf Model 46:1984–1995

    Article  CAS  PubMed  Google Scholar 

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  1. Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India, 136119

    Vipin Kumar & Himangini Bansal

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  1. Vipin Kumar
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  2. Himangini Bansal
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Correspondence to Vipin Kumar.

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Kumar, V., Bansal, H. QSAR studies on estimation of monoamine oxidase-A inhibitory activity using topological descriptors. Med Chem Res 20, 168–174 (2011). https://doi.org/10.1007/s00044-010-9302-9

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