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Synthesis and Identification of Small Compounds Active in Neurodegeneration, Part II

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 3713

Special Issue Editors


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Guest Editor
Department of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
Interests: antioxidants; bioactive compounds; small molecules; polyphenols; antibacterial activity; anticancer activity; medicinal chemistry; synthesis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Biomedical Research Center Seltersberg (BFS), Laboratory for Nutrition in Prevention and Therapy, Institute of Nutritional Sciences, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany
Interests: brain aging; neurodegenerative diseases; food-based prevention; pharmacological intervention; mitochondrial function
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Considering the success of the first Special Issue, it is our great pleasure to announce pleasure the second edition of “Synthesis and Identification of Small Compounds Active in Neurodegeneration, Part II”.

Keeping in mind the social impact of neurodegenerative diseases and the difficulty of identifying a single effective therapy, interest in creating scientific networks as a possibility for discovering new chemical entities remains active.

Due the high versatility of small molecules in terms of physiochemical properties, easier availability, various administration routes, and defined chemical structures, they play a central role in medicinal chemistry and represent promising drug candidates. Natural sources and chemical synthesis are two options for developing novel neuroprotective drug candidates. In particular, the rational combination of two or more chemical entities or synthetic modification of a common skeleton make them a favorable tool in rational design.

The main aim of this Special Issue is to collect and illustrate the latest developments in the field of the isolation, structural characterization, rational design, synthesis, and biological evaluation of compounds with low molecular weight related to neurodegenerative diseases.

We invite all researchers working in this field to contribute original articles and reviews covering the main aspects of the topic. We hope that this Special Issue will continue to provide a forum for thought-provoking ideas.

Dr. Barbara De Filippis
Prof. Dr. Gunter Peter Eckert
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • small active compounds
  • food chemistry
  • neurodegenerative diseases
  • medicinal and pharmaceutical chemistry
  • BBB
  • synthesis
  • nanoformulations

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Published Papers (1 paper)

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Research

25 pages, 3037 KiB  
Article
Resveratrol Analogues as Dual Inhibitors of Monoamine Oxidase B and Carbonic Anhydrase VII: A New Multi-Target Combination for Neurodegenerative Diseases?
by Simone Carradori, Marialuigia Fantacuzzi, Alessandra Ammazzalorso, Andrea Angeli, Barbara De Filippis, Salvatore Galati, Anél Petzer, Jacobus P. Petzer, Giulio Poli, Tiziano Tuccinardi, Mariangela Agamennone and Claudiu T. Supuran
Molecules 2022, 27(22), 7816; https://doi.org/10.3390/molecules27227816 - 13 Nov 2022
Cited by 16 | Viewed by 3273
Abstract
Neurodegenerative diseases (NDs) are described as multifactorial and progressive syndromes with compromised cognitive and behavioral functions. The multi-target-directed ligand (MTDL) strategy is a promising paradigm in drug discovery, potentially leading to new opportunities to manage such complex diseases. Here, we studied the dual [...] Read more.
Neurodegenerative diseases (NDs) are described as multifactorial and progressive syndromes with compromised cognitive and behavioral functions. The multi-target-directed ligand (MTDL) strategy is a promising paradigm in drug discovery, potentially leading to new opportunities to manage such complex diseases. Here, we studied the dual ability of a set of resveratrol (RSV) analogs to inhibit two important targets involved in neurodegeneration. The stilbenols 19 were tested as inhibitors of the human monoamine oxidases (MAOs) and carbonic anhydrases (CAs). The studied compounds displayed moderate to excellent in vitro enzyme inhibitory activity against both enzymes at micromolar/nanomolar concentrations. Among them, the best compound 4 displayed potent and selective inhibition against the MAO-B isoform (IC50 MAO-A 0.43 µM vs. IC50 MAO-B 0.01 µM) with respect to the parent compound resveratrol (IC50 MAO-A 13.5 µM vs. IC50 MAO-B > 100 µM). It also demonstrated a selective inhibition activity against hCA VII (KI 0.7 µM vs. KI 4.3 µM for RSV). To evaluate the plausible binding mode of 1–9 within the two enzymes, molecular docking and dynamics studies were performed, revealing specific and significant interactions in the active sites of both targets. The new compounds are of pharmacological interest in view of their considerably reduced toxicity previously observed, their physicochemical and pharmacokinetic profiles, and their dual inhibitory ability. Compound 4 is noteworthy as a promising lead in the development of MAO and CA inhibitors with therapeutic potential in neuroprotection. Full article
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