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Molecules 2017, 22(7), 1192; doi:10.3390/molecules22071192

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs

1
Biomedical Sciences Research Complex, University of St Andrews, St Andrews KY16 8QP, UK
2
School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 23 June 2017 / Revised: 10 July 2017 / Accepted: 11 July 2017 / Published: 15 July 2017
(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

Abstract

The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC50 value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behavior remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions. View Full-Text
Keywords: Alzheimer’s disease; l-deprenyl (selegiline); donepezil; galantamine; inhibitor constant; enzyme inhibition; multitarget-directed ligand (MTDL); rasagiline; rivastigmine Alzheimer’s disease; l-deprenyl (selegiline); donepezil; galantamine; inhibitor constant; enzyme inhibition; multitarget-directed ligand (MTDL); rasagiline; rivastigmine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ramsay, R.R.; Tipton, K.F. Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs. Molecules 2017, 22, 1192.

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