The Medicinal Chemistry of Natural and Semisynthetic Compounds against Parkinson’s and Huntington’s Diseases

Abstract

Among the diseases affecting the central nervous system (CNS), neurodegenerations attract the interest of both the clinician and the medicinal chemist. The increasing average age of population, the growing number of patients, and the lack of long-term effective remedies push ahead the quest for novel tools against this class of pathologies. We present a review on the state of the art of the molecules (or combination of molecules) of natural origin that are currently under study against two well-defined pathologies: Parkinson's disease (PD) and Huntington's disease (HD). Nowadays, very few tools are available for preventing or counteracting the progression of such diseases. Two major parameters were considered for the preparation of this review: particular attention was reserved to these research works presenting well-defined molecular mechanisms for the studied compounds, and where available, papers reporting in vivo data were preferred. A literature search for peer-reviewed articles using PubMed, Scopus, and Reaxys databases was performed, exploiting different keywords and logical operators: 91 papers were considered (preferentially published after 2015). The review presents a brief overview on the etiology of the studied neurodegenerations and the current treatments, followed by a detailed discussion of the natural and semisynthetic compounds dividing them in different paragraphs considering their several mechanisms of action.

Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics

“…In a molecular docking study, the MAO-A-inhibitory potential of baicalein and decursin; two compounds isolated from the roots of Scutellaria baicalensis was reported [99]. In recent research, secondary metabolites, including berberine, maackiain and 3-phenyl coumarins were identified as novel MAO-B inhibitors [101].…”

A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration

“…Several plant extracts and, more specifically, their bioactive constituents were reported to possess neuroprotective action and to improve cognitive function against dementia and other neurodegenerative disorders [25]. The activity of natural compounds ameliorating AD conditions in preclinical or clinical studies is generally related to a multi-target mechanism of action [26], and inhibition of one or more PDE isoforms is often involved [8,[27][28][29]. Natural, semi-synthetic, and synthetic compounds can in fact inhibit PDEs with different degrees of selectivity, as well as act as non-selective inhibitors [30].…”

“…Pharmaceuticals 2021, 14, x FOR PEER REVIEW 3 of 13 target mechanism of action [26], and inhibition of one or more PDE isoforms is often involved [8,[27][28][29]. Natural, semi-synthetic, and synthetic compounds can in fact inhibit PDEs with different degrees of selectivity, as well as act as non-selective inhibitors [30].…”

Antioxidant Potential of Psychotropic Drugs: From Clinical Evidence to In Vitro and In Vivo Assessment and toward a New Challenge for in Silico Molecular Design

“…Several classes of approved drugs have been studied through the years for their antioxidant properties [ 1 , 5 , 6 ]. Proton pump inhibitors [ 7 ], antidiabetics [ 8 ], drugs acting on the cardiovascular system [ 9 ], antiepileptics [ 10 ], and anti-inflammatory agents [ 11 ] represent some of the investigated classes, which are also paired by antioxidant natural and semi-synthetic compounds with biological activity [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Furthermore, besides therapeutic agents, it must be stressed that bioactive components from diet have been recognized among the risk factors or, on the other hand, protective agents possibly influencing oxidative stress and pathogenesis of related diseases [ 20 , 21 ].…”