Synthetic and Natural Monoamine Oxidase Inhibitors as Potential Lead Compounds for Effective Therapeutics

Abstract

Monoamine oxidases A and B (MAO-A and B) play a critical role in the metabolism of intracellular neurotransmitters of the central nervous system. For decades, MAO inhibitors have proven their clinical efficacy as potential drug targets for several neurological and neurodegenerative diseases. Use of first generation non selective MAO inhibitors as neuropsychiatric drugs elicited several side effects like hypertensive crisis and cheese reaction. Therefore their use is now limited due to non-selectivity towards MAO isoforms and inhibition of metabolizing enzymes like cytochrome P450. Development of selective and specific MAO inhibitors like moclobemide, toloxatone improves their efficacy as disease-modifying effects in monotherapy as well as adjunctive therapy. Recently a lot of research has been done to elucidate the pharmacological potential of medicinal plants and their isolated bioactive constituents having MAO inhibitory activity. Herbs containing MAO inhibitors are extensively used for the development of potent synthetic drugs and as safe and effective alternatives to the available synthetic drugs in the treatment of neurodegenerative diseases such as depression, Parkinson and Alzheimer's. In several diseases like Parkinson natural MAO inhibitors prevented the neuron denaturalization by their dual action via enhancing neurotransmission of dopamine as well as lowering the generation of free radicals and toxins. Currently development of selective MAO inhibitors is still under study to achieve more effective therapies by using Computer Aided Drug Designing, Ligand-based models and structure-activity hypothesis. These approaches also facilitate understanding the interaction of newly designed molecule with MAO enzymes and the rationalization of probable mechanisms of action.

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

“…[124][125][126][127][128][129][130] Phyto-bioactive compounds have shown an excellent anti-neuroinflammatory effect through various pathways. [131][132][133][134][135][136][137][138][139][140][141] However, they have limitations in oral delivery due to their extensive first-pass metabolism and difficulty in crossing the blood-brain barrier. Recently, SLN-loaded phyto-bioactive compounds have shown excellent bioavailability through oral delivery and a higher brain bioavailability.…”

Design, synthesis, in vitro and in silico evaluation of new pyrrole derivatives as monoamine oxidase inhibitors

“…The altered concentrations of the neurotransmitters in the brain are linked with the pathology of various neurological disorders including depression, Parkinson's disease (PD) and Alzheimer's disease (AD) and both MAO isoforms are involved in the pathogenesis of these diseases due to their pivotal role in key physiological processes. As a result, MAO has attracted a great deal of interest as a promising target for the development of central nervous system (CNS) agents …”

“…Selective MAO‐A inhibitors are being developed as drug candidates for the management of depression and anxiety disorders. On the other hand, selective MAO‐B inhibitors are found to be effective for the treatment of PD and AD with a better safety profile as compared to nonselective MAO inhibitors …”

The p38-MAPK Pathway Is Involved in Neuroprotection of Artemisinin against H2O2-induced Apoptosis in PC12 Cells

“…In the recent past, increasing attention has been paid towards harnessing the antioxidant potential of natural products and compounds extracted from plants which has higher efficacy and lower side effects in general [11,13]. Artemisinin, a sesquiterpene lactone, was originally extracted from the qinghao by a female Chinese scientist, and has become one of the most famous chemical in the world [14].…”