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Review
. 2022 May 5;7(19):16244-16259.
doi: 10.1021/acsomega.2c01470. eCollection 2022 May 17.

Exploration of the Detailed Structure-Activity Relationships of Isatin and Their Isomers As Monoamine Oxidase Inhibitors

Sunil Kumar  1 , Aathira Sujathan Nair  1 , Mohamed A Abdelgawad  2 , Bijo Mathew  1
Affiliations
Review

Exploration of the Detailed Structure-Activity Relationships of Isatin and Their Isomers As Monoamine Oxidase Inhibitors

Sunil Kumar et al. ACS Omega. .

Abstract

Monoamine oxidase (MAO) is a protein with a key function in the catabolism of neuroamines in both central and peripheral parts of the body. MAO-A and -B are two isozymes of this enzyme which have emerged to be considered as a drug target for the treatment of neurodenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Isatin is an endogenous small fragment, reversible inhibitor for MAO enzymes and is more selective for MAO-B than -A. Isatin is responsible for increasing the dopamine level in the brain by the inhibition of an MAO enzyme. The very few selective and reversible inhibitors existing for MAO proteins and the intensity of neurological diseases in humanity have opened a new door for researchers. Isatin has a polypharmacological profile in medicinal chemistry, is a reversible inhibitor for both the MAOs, and shows high selectivity potent inhibition for MAO-B. In this review, we discuss isatins and their analogues phthalide and phthalimide with structure-activity relationships (SARs), and this comprehensive information accelerates the ideas for design and development of a new class of MAO inhibitors for neurodegenerative diseases.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Structure of isatins and their reactions.
Figure 2
Figure 2
Structure of MAO inhibitors.
Figure 3
Figure 3
Structure of an indole-based nucleus (isatin derivative).
Figure 4
Figure 4
Structure–activity relationship of isatin derivatives.
Figure 5
Figure 5
Structure of styryl-based isatin derivatives.
Figure 6
Figure 6
(a) Structures of benzyloxy- and benzal-based isatin derivatives. (b) Compound 11 with MAO-B interaction.
Figure 7
Figure 7
Structure–activity relationship for benzyloxy- and benzal-based isatin derivatives.
Figure 8
Figure 8
Structure of phthalimide-based derivative.
Figure 9
Figure 9
Reference molecules for MAO study.
Figure 10
Figure 10
Structure–activity relationship for phthalimide-based derivatives.
Figure 11
Figure 11
(a) Structure–activity relationship for C-5 and C-6 styryl-based isatin derivatives. (b) Compound 7 with MAO-B interactions.
Figure 12
Figure 12
Structure of a potent molecule of phthalimide derivative 37.
Figure 13
Figure 13
Structure–activity relationship for benzylsulfinyl-based phthalimide derivatives.
Figure 14
Figure 14
Structure of phthalide-based derivative.
Figure 15
Figure 15
Structure–activity relationship for phthalide-based derivatives.
Figure 16
Figure 16
Structure of phenacyloxindole analogues
Figure 17
Figure 17
Structure–activity relationship for phenacyloxindoles based isatin derivatives.
Figure 18
Figure 18
(a) Structure of phenylsulfonyl-based isatin derivatives. (b) Interaction with MAO-B and compound 65.
Figure 19
Figure 19
Structure–activity relationship for phenylsulfonyl-based isatin derivatives.
Figure 20
Figure 20
Structure of piperonylic acid based isatin derivatives.
Figure 21
Figure 21
Structure–activity relationship and interaction with MAO-B for piperonylic acid based isatin derivatives on MAO inhibition.
Figure 22
Figure 22
(a) Structure of imino-based isatin derivatives. (b) Compound 76 with MAO-B interactions.
Figure 23
Figure 23
Structure of isatin-based differently derived scaffolds.
Figure 24
Figure 24
Structure of benzyloxy-based isatin derivatives.
Figure 25
Figure 25
Structure–activity relationship for benzyloxy-based isatin derivatives.
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