Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors.

Abstract

Parkinson's disease is a neurodegenerative condition characterized by slow movement (bradykinesia), tremors, and muscle stiffness. These symptoms occur due to the degeneration of dopamine- producing neurons in the substantia nigra region of the brain, leading to reduced dopamine levels. The development of Parkinson's Disease (PD) involves a combination of genetic and environmental factors. PD is associated with abnormal regulation of the monoamine oxidase (MAO) enzyme. Monoamine oxidase inhibitors (MAOIs) are an important class of drugs used to treat PD and other neurological disorders. In the early stages of PD, monotherapy with MAO-B inhibitors has been shown to be both safe and effective. These inhibitors are also commonly used as adjuncts in long-term disease management, as they can improve both motor and non-motor symptoms, reduce "OFF" periods, and potentially slow disease progression. However, current MAO-B inhibitors come with side effects like dizziness, nausea, vomiting, light-headedness, and fainting. Therefore, accelerating the development of new MAO-B inhibitors with fewer side effects is crucial. This review explores natural compounds that may inhibit monoamine oxidase B (MAO-B), focusing on key findings from the past seven years. It highlights the most effective heterocyclic compounds against MAO-B, including thiazolyl hydrazone, pyridoxine-resveratrol, pyridazine, isoxazole, oxadiazole, benzothiazole, benzoxazole, coumarin, caffeine, pyrazoline, piperazine, piperidine, pyrrolidine, and morpholine derivatives. The review covers in vitro, in silico, and in vivo data, along with the structure- activity relationship of these compounds. These findings offer valuable insights for the development of more effective MAO-B inhibitors and advancements in Parkinson's disease research.