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Drug Candidates for the Treatment of Alzheimer’s and Parkinson’s Disease

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 5897

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Special Issue Information

Dear Colleagues,

During the last three decades, neurodegenerative diseases and dementia, especially Alzheimer’s (AD) and Parkinson’s (PD) diseases, have been recognized as some of the most challenging issues for medicinal chemistry, pharmacology, and all other health- and drug-related sciences, due to their multifactorial and complex pathophysiology, severity, high social–economic impacts. With longevity being one of the most important risk factors, all available statistical data agree that in the coming three decades, as the world population becomes older, the number of patients with one of these incapacitant diseases will reach an exponential increase unless we are able to discover novel disease-modifying drugs or effective cures. In this context, a great number of scientists working in academia and the pharma industry have dedicated their efforts to the design, synthesis, and evaluation of new small molecules that could act as genuine and innovative drug candidates addressed to the multifactorial-related biochemical and cellular changes related to the onset, progression and severity of neurodegeneration. Thus, the aim of this Special Issue is to collect high-impact scientific contributions, representing the most outstanding up-to-date results and new findings related to the discovery of novel chemical entities with potential druggability and therapeutical value for the treatment of AD and PD.

Dr. Cláudio Viegas-Junior
Prof. Dr. Andrea Tarozzi
Guest Editors

Manuscript Submission Information

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Keywords

Alzheimer’s disease
Parkinson’s disease
multitarget directed ligands
multifunctional ligands
neurodegeneration
neuroinflammation
neuroprotection
neurodegenerative diseases
brain disorders
dementia

Published Papers (2 papers)

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Research

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12 pages, 2914 KiB

Open AccessArticle

Development of Halogenated-Chalcones Bearing with Dimethoxy Phenyl Head as Monoamine Oxidase-B Inhibitors

by Nisha Abdul Rehuman, Jong Min Oh, Mohamed A. Abdelgawad, Eman A. M. Beshr, Mohammed A. S. Abourehab, Nicola Gambacorta, Orazio Nicolotti, Rakesh Kumar Jat, Hoon Kim and Bijo Mathew

Pharmaceuticals 2022, 15(9), 1152; https://doi.org/10.3390/ph15091152 - 16 Sep 2022

Cited by 11 | Viewed by 1758

Abstract

Two series of dimethoxy-halogenated chalcones (DM1–DM20) were synthesized and tested for their ability to inhibit monoamine oxidase (MAOs). Compound DM2 exhibited the most significant inhibition against MAO-B with an IC₅₀ value of 0.067 µM, followed by compound DM18 (IC₅₀ = 0.118 µM), with selectivity index (SI) values of 93.88 and >338.98, respectively. However, none of the substances successfully inhibited MAO-A. The MAO-B inhibitors DM2 and DM18 were competitive and reversible, with K_i values of 0.032 ± 0.004 and 0.045 ± 0.001 µM, respectively. DM2 was non-toxic below 100 µg/mL in the cytotoxic test using the Vero epithelial cell line by the MTT method. According to molecular docking studies, DM2 and DM18 formed very similar conformations within the MAO-B binding pocket, with the ortho-chlorine and ortho-fluorine aromatic rings sandwiched between F168 and Y326. These conformations were predicted to show better interactions with the targeted MAO-B than MAO-A. In particular, the induced-fit docking of the dimethoxy phenyl ring of DM2 facing the hydrophobic pocket made up of FAD, Y398, and Y435 had an impact on F168 in the docking pocket. Taken together, DM2 and DM18 may be suitable candidates for treating neurodegenerative conditions such as Parkinson’s disease. Full article

(This article belongs to the Special Issue Drug Candidates for the Treatment of Alzheimer’s and Parkinson’s Disease)

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Review

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36 pages, 14363 KiB

Open AccessReview

Chalcones as Potential Ligands for the Treatment of Parkinson’s Disease

by Ewelina Królicka, Katarzyna Kieć-Kononowicz and Dorota Łażewska

Pharmaceuticals 2022, 15(7), 847; https://doi.org/10.3390/ph15070847 - 10 Jul 2022

Cited by 10 | Viewed by 3584

Abstract

Along with the increase in life expectancy, a significant increase of people suffering from neurodegenerative diseases (ND) has been noticed. The second most common ND, after Alzheimer’s disease, is Parkinson’s disease (PD), which manifests itself with a number of motor and non-motor symptoms that hinder the patient’s life. Current therapies can only alleviate those symptoms and slow down the progression of the disease, but not effectively cure it. So now, in addition to understanding the mechanism and causes of PD, it is also important to find a powerful way of treatment. It has been proved that in the etiology and course of PD, the essential roles are played by dopamine (DA) (an important neurotransmitter), enzymes regulating its level (e.g., COMT, MAO), and oxidative stress leading to neuroinflammation. Chalcones, due to their “simple” structure and valuable biological properties are considered as promising candidates for treatment of ND, also including PD. Here, we provide a comprehensive review of chalcones and related structures as potential new therapeutics for cure and prevention of PD. For this purpose, three databases (Pubmed, Scopus and Web of Science) were searched to collect articles published during the last 5 years (January 2018–February 2022). Chalcones have been described as promising enzyme inhibitors (MAO B, COMT, AChE), α-synuclein imaging probes, showing anti-neuroinflammatory activity (inhibition of iNOS or activation of Nrf2 signaling), as well as antagonists of adenosine A₁ and/or A_2A receptors. This review focused on the structure–activity relationships of these compounds to determine how a particular substituent or its position in the chalcone ring(s) (ring A and/or B) affects biological activity. Full article

(This article belongs to the Special Issue Drug Candidates for the Treatment of Alzheimer’s and Parkinson’s Disease)

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