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

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.

Total Synthesis and Monoamine Oxidase Inhibitory Activities of (±)-Entonalactam A and Its Derivatives

“…There are two isoforms of MAO (MAO-A and MAO-B). , The MAO-A inhibitor moclobemide is a moderately effective antidepressant drug, and the MAO-B inhibitors selegiline and resagiline are globally approved treatments for Parkinson’s disease . Kumar et al reported the structure–activity relationships for MAO-A and -B inhibitors . In this report, isoindoline 1,3-dione, which shares a common structure with isoindolinones, and phthalide derivatives were evaluated.…”

“…In this report, isoindoline 1,3-dione, which shares a common structure with isoindolinones, and phthalide derivatives were evaluated. Substitution at C-5 of isoindoline 1,3-dione or phthalides increased the inhibitory activity of MAO-A and MAO-B . Thus, isoindolinones and phthalides isolated from Xylariaceae may show MAO inhibitory activity.…”

“…Substitution at C-5 of isoindoline 1,3-dione or phthalides increased the inhibitory activity of MAO-A and MAO-B. 9 Thus, isoindolinones and phthalides isolated from Xylariaceae may show MAO inhibitory activity. In this study, we developed a synthetic strategy for the total synthesis of (±)-entonalactam A (6) and its analogues.…”

“… 8 Kumar et al reported the structure–activity relationships for MAO-A and -B inhibitors. 9 In this report, isoindoline 1,3-dione, which shares a common structure with isoindolinones, and phthalide derivatives were evaluated. Substitution at C-5 of isoindoline 1,3-dione or phthalides increased the inhibitory activity of MAO-A and MAO-B.…”

Synthesis and Potential Dual Inhibitory Activity Against Acetylcholinesterase and Butyrylcholinesterase of Galactose‐Conjugated Isatin β‐Thiosemicarbazones

“…Isatin (1 H ‐indoline‐2,3‐dione) and many of its derivatives exhibit a broad spectrum of biological activities, including activity on the CNS and in chemotherapy [12] . Some of the biological activities of isatin‐ring‐containing derivatives commonly mentioned in references include anticonvulsants, [13] sedatives and hypnosis, [14] monoamine oxidase inhibitors, [12a] antiviral, [15] antioxidant, [16] anticancer, [17] anti‐mycobacterial, [18] and antibacterial activity, [19] etc. Additionally, several derivatives of isatin have been synthesized and probed for inhibitory activity of AChE and BChE enzymes, [20] including hydrazones [21] and (thio)semicarbazones [22] .…”