Abstract
The quantitative structure-activity relationship method based on the three-dimensional structure of the target molecules (3D-QSAR) represents a valuable predictive tool for the design of new bioactive agents. Herewith, a detailed procedure is described which uses a pool comprising 67 derivatives substituted at position 4 and 7 of the common coumarin scaffold as a benchmark for deriving a predictive 3D-QSAR model employed for guiding the rational design of 10 new potent and selective MAO B inhibitors.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Nicolotti O, Carotti A (2006) QSAR and QSPR studies of a highly structured physicochemical domain. J Chem Inf Model 46:264–276
Hansch C, Leo A, Hoekman DH (eds) (1995) Exploring QSAR: hydrophobic, electronic, and steric constants. American Chemical Society, Washington, DC
Goodford PJA (1985) Computational procedure for determining energetically favorable binding sites on biologically important macromolecules. J Med Chem 28:849–857
Nicolotti O, Miscioscia TF, Carotti A, Leonetti F, Carotti A (2008) An integrated approach to ligand- and structure-based drug design: development and application to a series of serine protease inhibitors. J Chem Inf Model 48:1211–1226
Nicolotti O, Giangreco I, Miscioscia TF, Carotti A (2009) Improving quantitative structure-activity relationships through multiobjective optimization. J Chem Inf Model 49:2290–2302
Cramer RD (1993) Partial least squares (PLS): its strengths and limitations. Persp Drug Discovery Design 1:269–278
Doweyko AM (2004) 3D-QSAR Illusions. J Comput Aided Mol Des 18:587–596
Pisani L, Farina R, Nicolotti O, Gadaleta D, Soto-Otero R, Catto M, Di Braccio M, Mendez-Alvarez E, Carotti A (2015) In Silico design of novel 2H-Chromen-2-one derivatives as potent and selective MAO-B inhibitors. Eur J Med Chem 89:98–105
SYBYL, Version 7.1; Tripos Inc. (1699 South Hanley Road, St. Louis, MO 63144)
Martí-Renom MA, Stuart AC, Fiser A, Sánchez R, Melo F, Šali A (2000) Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct 29:291–325
LigPrep, Version 2.3, Schrödinger, LLC, New York, NY, 2009
Phase, Version 3.1, Schrodinger, LLC, New York, NY, 2009
Binda C, Wang J, Pisani L, Caccia C, Carotti A, Salvati P, Edmondson DE, Mattevi A (2007) Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and Coumarin analogs. J Med Chem 50:5848–5852
Cruciani G (ed) (2006) Molecular interaction fields: applications in drug discovery and ADME prediction. Wiley, London
Banks JL, Beard HS, Cao Y, Cho AE, Damm W, Farid R, Felts AK, Halgren TA, Mainz DT, Maple JR, Murphy R, Philipp DM, Repasky MP, Zhang LY, Berne BJ, Friesner RA, Gallicchio E, Levy RM (2005) Integrated modeling program, applied chemical theory (IMPACT). J Comput Chem 26:1752–1780
Ghose AK, Viswanadhan VN, Wendoloski JJ (1998) Prediction of hydrophobic (lipophilic) properties of small organic molecules using fragmental methods: an analysis of ALOGP and CLOGP methods. J Phys Chem A 102:3762–3772
Todeschini R, Consonni V (2009) Molecular descriptors for chemoinformatics: volume I: alphabetical listing / volume II: appendices, references. Wiley, weinheim
Catto M, Nicolotti O, Leonetti F, Carotti A, Favia AD, Soto-Otero R, Méndez-Álvarez E, Carotti A (2006) Structural insights into monoamine oxidase inhibitory potency and selectivity of 7-substituted Coumarins from ligand- and target-based approaches. J Med Chem 49:4912–4925
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Gambacorta, N., Catto, M., Pisani, L., Carotti, A., Nicolotti, O. (2023). Informed Use of 3D-QSAR for the Rational Design of Coumarin Derivatives as Potent and Selective MAO B Inhibitors. In: Binda, C. (eds) Monoamine Oxidase. Methods in Molecular Biology, vol 2558. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2643-6_15
Download citation
DOI: https://doi.org/10.1007/978-1-0716-2643-6_15
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2642-9
Online ISBN: 978-1-0716-2643-6
eBook Packages: Springer Protocols