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Special Issue "Recent Drug Design Strategy of the Design of Molecules against Alzheimer’s Disease and Parkinson’s Disease"

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

Deadline for manuscript submissions: closed (15 November 2021).

Special Issue Editors

Dr. Bijo Mathew
E-Mail Website
Guest Editor
Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India
Interests: drug discovery of neurodegenerative disorders; cancer and molecular modelling
Prof. Dr. Orazio Nicolotti
E-Mail Website
Guest Editor
Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “Aldo Moro”, Bari, Italy
Interests: drug design; QSAR; predictive toxicology; combinatorial library design; evolutionary algorithms; docking and molecular dynamics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most prevalent of the heterogeneous and complex neurodegenerative disorders (NDDs) that largely affect the elderly patients. Their pathogenesis has been attributed to a variety of genomic, epigenomic, and environmental factors. Mounting evidence indicates that drugs targeting a single pathway cannot adequately address the multifactorial nature of NDDs. Oxidative stress, mitochondrial dysfunction, and imbalances in the levels of enzymes that control the metabolism of biogenic amines may promote NDD progression. On the other hand, several molecular scaffolds have been designed to simultaneously target entities such as choline esterase (ChE), monoamine oxidases (MAOs), and β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE-1), to retard NDD progression.

Topics to be covered include the following:

  • Multi-target design of the molecules for AD;
  • Multi-target design of the molecules for PD;
  • Natural isolates for AD and PD;
  • Synthesis and Biological evaluation for the treatment of AD and PD.

Dr. Bijo Mathew
Prof. Dr. Orazio Nicolotti
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 papers will be 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. 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 2000 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

  • Alzheimer’s disease
  • Parkinson’s disease
  • choline esterase
  • monoamine oxidases
  • β-site amyloid precursor
  • β-secretase

Published Papers (1 paper)

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Research

Article
Selected Class of Enamides Bearing Nitro Functionality as Dual-Acting with Highly Selective Monoamine Oxidase-B and BACE1 Inhibitors
Molecules 2021, 26(19), 6004; https://doi.org/10.3390/molecules26196004 - 03 Oct 2021
Viewed by 481
Abstract
A small series of nitro group-bearing enamides was designed, synthesized (NEA1NEA5), and evaluated for their inhibitory profiles of monoamine oxidases (MAOs) and β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE1). Compounds NEA3 and NEA1 exhibited a more potent [...] Read more.
A small series of nitro group-bearing enamides was designed, synthesized (NEA1NEA5), and evaluated for their inhibitory profiles of monoamine oxidases (MAOs) and β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE1). Compounds NEA3 and NEA1 exhibited a more potent MAO-B inhibition (IC50 value = 0.0092 and 0.016 µM, respectively) than the standards (IC50 value = 0.11 and 0.14 µM, respectively, for lazabemide and pargyline). Moreover, NEA3 and NEA1 showed greater selectivity index (SI) values toward MAO-B over MAO-A (SI of >1652.2 and >2500.0, respectively). The inhibition and kinetics studies suggested that NEA3 and NEA1 are reversible and competitive inhibitors with Ki values of 0.013 ± 0.005 and 0.0049 ± 0.0002 µM, respectively, for MAO-B. In addition, both NEA3 and NEA1 showed efficient BACE1 inhibitions with IC50 values of 8.02 ± 0.13 and 8.21 ± 0.03 µM better than the standard quercetin value (13.40 ± 0.04 µM). The parallel artificial membrane permeability assay (PAMPA) method demonstrated that all the synthesized derivatives can cross the blood–brain barrier (BBB) successfully. Docking analyses were performed by employing an induced-fit docking approach in the GLIDE module of Schrodinger, and the results were in agreement with their in vitro inhibitory activities. The present study resulted in the discovery of potent dual inhibitors toward MAO-B and BACE1, and these lead compounds can be fruitfully explored for the generation of newer, clinically active agents for the treatment of neurodegenerative disorders. Full article
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