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Pharmaceuticals
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Pharmacotherapy of Neurodegeneration Disorders
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Pharmacotherapy of Neurodegeneration Disorders

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

Deadline for manuscript submissions: 28 February 2025 | Viewed by 3783

Special Issue Editors

Prof. Dr. Magdalena Kondeva-Burdina

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Guest Editor
Laboratory “Drug metabolism and drug toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, Sofia, Bulgaria
Interests: neuroprotection; neuroinflammation; oxidative stress; antioxidant activity; MAO inhibition; hepatotoxicity; neurotoxicity; biotransformation
Special Issues, Collections and Topics in MDPI journals
Dr. Maya Georgieva

E-Mail Website
Guest Editor
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University-Sofia, Sofia, Bulgaria
Interests: medicinal chemistry; pharmaceutical chemistry; organic synthesis; heterocycles; drug design and discovery; synthesis and structure-activity relationships of biologically active compounds (small molecules); drug metabolism; pharmacokinetics; pharmacodynamics; drug analysis; chromatography
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A significant increase in the ageing of populations worldwide is especially prevalent in recent decades, with age-related rates steadily increasing. The progressive degeneration and/or death of neuronal cells, resulting in the manifestation of motor (ataxia) and mental disorders (dementia), is linked to a number of neurodegenerative diseases, characterized by the loss of neurons in certain areas of the brain. The current therapeutic strategies in neurodegenerative diseases are mainly aimed at influencing various symptoms, where increasing interest is paid to the key role of oxidative stress and inflammatory processes in the pathogenesis of neurodegenerative diseases. In this relationship, the isolation or synthesis of various biologically active molecules with potential anti-inflammatory and antioxidant effects would expand approaches for the therapy of these diseases beyond conventional treatment, which is accompanied by the manifestation of a number of adverse drug reactions. In addition, the search and the design of new chemically available multitarget agents will add to the search for contemporaneous strategies in neurodegenerative tratment.

Prof. Dr. Magdalena Kondeva-Burdina
Prof. Dr. Maya Georgieva
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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

  • neurodegeneration
  • inflammation
  • oxidative stress
  • neuroprotection
  • new biologically active molecules
  • heterocycles
  • synthesis
  • in silico drug design
  • pyrrole
  • MW-assisted synthesis
  • pharmaceutical chemistry

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Published Papers (2 papers)

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Research

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24 pages, 3471 KiB  
Article
Novel Pyrrole Derivatives as Multi-Target Agents for the Treatment of Alzheimer’s Disease: Microwave-Assisted Synthesis, In Silico Studies and Biological Evaluation
by Emilio Mateev, Valentin Karatchobanov, Marjano Dedja, Konstantinos Diamantakos, Alexandrina Mateeva, Muhammed Tilahun Muhammed, Ali Irfan, Magdalena Kondeva-Burdina, Iva Valkova, Maya Georgieva and Alexander Zlatkov
Pharmaceuticals 2024, 17(9), 1171; https://doi.org/10.3390/ph17091171 - 4 Sep 2024
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Abstract
Considering the complex pathogenesis of Alzheimer’s disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding [...] Read more.
Considering the complex pathogenesis of Alzheimer’s disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding hydrazide–hydrazones (vh1-4) were synthesized by applying highly efficient MW-assisted synthetic protocols. The synthetic pathway provided excellent yields and reduced reaction times under microwave conditions compared to conventional heating. The biological assays indicated that most of the novel pyrroles are selective MAO-B inhibitors with IC50 in the nanomolar range (665 nM) and moderate AChE inhibitors. The best dual-acting MAO-B/AChE inhibitor (IC50 hMAOB–0.665 μM; IC50 eeAChE—4.145 μM) was the unsubstituted pyrrole-based hydrazide (vh0). Importantly, none of the novel molecules displayed hMAOA-blocking capacities. The radical-scavenging properties of the compounds were examined using DPPH and ABTS in vitro tests. Notably, the hydrazide vh0 demonstrated the best antioxidant activities. In addition, in silico simulations using molecular docking and MM/GBSA, targeting the AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z), were utilized to obtain active conformations and to optimize the most prominent dual inhibitor (vh0). The ADME and in vitro PAMPA studies demonstrated that vh0 could cross the blood–brain barrier, and it poses good lead-like properties. Moreover, the optimized molecular structures and the frontier molecular orbitals were examined via DFT studies at 6-311G basis set in the ground state. Full article
(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)
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Review

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42 pages, 5459 KiB  
Review
Emerging Perspectives on Prime Editor Delivery to the Brain
by Eli BenDavid, Sina Ramezanian, Yaoyao Lu, Joël Rousseau, Avi Schroeder, Marc Lavertu and Jacques P. Tremblay
Pharmaceuticals 2024, 17(6), 763; https://doi.org/10.3390/ph17060763 - 11 Jun 2024
Viewed by 1997
Abstract
Prime editing shows potential as a precision genome editing technology, as well as the potential to advance the development of next-generation nanomedicine for addressing neurological disorders. However, turning in prime editors (PEs), which are macromolecular complexes composed of CRISPR/Cas9 nickase fused with a [...] Read more.
Prime editing shows potential as a precision genome editing technology, as well as the potential to advance the development of next-generation nanomedicine for addressing neurological disorders. However, turning in prime editors (PEs), which are macromolecular complexes composed of CRISPR/Cas9 nickase fused with a reverse transcriptase and a prime editing guide RNA (pegRNA), to the brain remains a considerable challenge due to physiological obstacles, including the blood–brain barrier (BBB). This review article offers an up-to-date overview and perspective on the latest technologies and strategies for the precision delivery of PEs to the brain and passage through blood barriers. Furthermore, it delves into the scientific significance and possible therapeutic applications of prime editing in conditions related to neurological diseases. It is targeted at clinicians and clinical researchers working on advancing precision nanomedicine for neuropathologies. Full article
(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)
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