A large plethora of drugs and promising lead compounds contain halogens in their structures. The introduction of such moieties strongly modulates their physical-chemical features as well as pharmacokinetic and pharmacodynamic profile. The most important outcome was shown to be the ability of these halogens to favourably influence the drug-target interaction and energetic stability within the active site by the establishment of halogen bonds. This review attempted to demonstrate the key role exerted by these versatile moieties when correctly located in an organic scaffold to display Monoamine Oxidase (MAO) inhibition and selectivity towards the B isoform of this important enzyme. Human MAOs are well-recognized as therapeutic targets for mood disorders and neurodegenerative diseases and medicinal chemists were prompted to discover the structural requirements crucial to discriminate the slight differences between the active sits of the two isoforms (MAO-A and MAOB). The analysis of the structure-activity relationships of the most important scaffolds (hydrazothiazoles, coumarins, chromones, chalcones, pyrazolines) and the impact of halogen (F, Cl, Br and I) insertion on this biological activity and isozyme selectivity have been reported being a source of inspiration for the medicinal chemists.

New aspects of monoamine oxidase b inhibitors: The key role of halogens to open the golden door

Carradori S.
;
2021-01-01

Abstract

A large plethora of drugs and promising lead compounds contain halogens in their structures. The introduction of such moieties strongly modulates their physical-chemical features as well as pharmacokinetic and pharmacodynamic profile. The most important outcome was shown to be the ability of these halogens to favourably influence the drug-target interaction and energetic stability within the active site by the establishment of halogen bonds. This review attempted to demonstrate the key role exerted by these versatile moieties when correctly located in an organic scaffold to display Monoamine Oxidase (MAO) inhibition and selectivity towards the B isoform of this important enzyme. Human MAOs are well-recognized as therapeutic targets for mood disorders and neurodegenerative diseases and medicinal chemists were prompted to discover the structural requirements crucial to discriminate the slight differences between the active sits of the two isoforms (MAO-A and MAOB). The analysis of the structure-activity relationships of the most important scaffolds (hydrazothiazoles, coumarins, chromones, chalcones, pyrazolines) and the impact of halogen (F, Cl, Br and I) insertion on this biological activity and isozyme selectivity have been reported being a source of inspiration for the medicinal chemists.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/741267
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