Abstract
Hansch-type regression analysis enables the derivation of quantitative structure-activity relationship (QSAR) equations correlating bioactivity data with physicochemical parameters accounting for hydrophobicity, electronic properties, and steric effects of molecules or functional groups (substituents). Two datasets of MAO A and B inhibitors were enrolled in prototypical workflows employing multiparametric stepwise regression analysis, which includes linear and nonlinear (generally quadratic) terms. The optimal choice of variables (and/or combinations thereof) along with statistical validation yielded two robust equations describing MAO B potency and B/A selectivity, which included three and one parameter(s), respectively, and explained more than 80% of y-variance (r2) with low standard deviation (s) and good statistical significance (F, Fisher value).
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
Iacovino LG, Manzella N, Resta J, Vanoni MA, Rotilio L, Pisani L, Edmondson DE, Parini A, Mattevi A, Mialet-Perez J, Binda C (2020) Rational redesign of monoamine oxidase a into a dehydrogenase to probe ROS in cardiac aging. ACS Chem Biol 15:1795–1800
Pisani L, Iacobazzi RM, Catto M, Rullo M, Farina R, Denora N, Cellamare S, Altomare CD (2019) Investigating alkyl nitrates as nitric oxide releasing precursors of multitarget acetylcholinesterase-monoamine oxidase B inhibitors. Eur J Med Chem 161:292–309
Hong R, Li X (2019) Discovery of monoamine oxidase inhibitors by medicinal chemistry approaches. Medchemcomm 10:10–25
Tripathi AC, Upadhyay S, Paliwal S, Saraf SK (2018) Privileged scaffolds as MAO inhibitors: retrospect and prospects. Eur J Med Chem 145:445–497
Kubinyi H (1997) QSAR and 3D QSAR in drug design Part 1: methodology. Drug Discov Today 2:457–467
Ragno R, Esposito V, Di Mario M, Masiello S, Viscovo M, Cramer RD (2020) Teaching and learning computational drug design: student investigations of 3D quantitative structure-activity relationships through web applications. J Chem Educ 97:1922–1930
Verma J, Khedkar V, Coutinho E (2010) 3D-QSAR in Drug Design – A Review. Curr Top Med Chem 10:95–115
Cramer RD, Patterson DE, Bunce JD (1988) Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110:5959–5967
Morón JA, Campillo M, Perez V, Unzeta M, Pardo L (2000) Molecular determinants of MAO selectivity in a series of indolylmethylamine derivatives: biological activities, 3D-QSAR/CoMFA analysis, and computational simulation of ligand recognition. J Med Chem 43:1684–1691
Mathew B, Adeniyi AA, Dev S, Joy M, Ucar G, Mathew GE, Singh-Pillay A, Soliman ME (2017) Pharmacophore-based 3D-QSAR analysis of thienyl chalcones as a new class of human MAO-B inhibitors: investigation of combined quantum chemical and molecular dynamics approach. J Phys Chem B 121:1186–1203
Ekins S, Waller CL, Swaan PW, Cruciani G, Wrighton SA, Wikel JH (2000) Progress in predicting human ADME parameters in silico. J Pharmacol Toxicol Methods 44:251–272
Free SM, Wilson JW (1964) A mathematical contribution to structure-activity studies. J Med Chem 7:395–399
Hansch C, Fujita T (1964) P -σ-π analysis. A method for the correlation of biological activity and chemical structure. J Am Chem Soc 86:1616–1626
Altomare C, Cellamare S, Summo L, Catto M, Carotti A, Thull U, Carrupt PA, Testa B, Stoeckli-Evans H (1998) Inhibition of monoamine oxidase-B by condensed pyridazines and pyrimidines: effects of lipophilicity and structure−activity relationships. J Med Chem 41:3812–3820
Gnerre C, Catto M, Leonetti F, Weber P, Carrupt PA, Altomare C, Carotti A, Testa B (2000) Inhibition of monoamine oxidases by functionalized coumarin derivatives: biological activities, QSARs, and 3D-QSARs. J Med Chem 43:4747–4758
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
Pisani, L., de Candia, M., Rullo, M., Altomare, C.D. (2023). Hansch-Type QSAR Models for the Rational Design of MAO Inhibitors: Basic Principles and Methodology. 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_16
Download citation
DOI: https://doi.org/10.1007/978-1-0716-2643-6_16
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