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Molecules
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Nitric Oxide Modulators in Health and Disease II
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Nitric Oxide Modulators in Health and Disease II

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

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 6636

Special Issue Editors

Dr. Cristina Maccallini

E-Mail Website
Guest Editor
Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
Interests: medicinal chemistry; synthesis and biological evaluation of new small molecules for the therapy of cancer; inflammatory diseases and infections; extraction of bioactive compounds from natural sources
Special Issues, Collections and Topics in MDPI journals
Dr. Rosa Amoroso

E-Mail Website
Guest Editor
Department of Pharmacy, University of G. d\'Annunzio of Chieti and Pescara, Chieti, Italy
Interests: medicinal chemistry; organic synthesis; nitric oxide; nitric oxide synthase; PPAR receptors; metabolic syndrome; aromatase inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

About 40 years ago, the first paper on the endothelium-dependent relaxation factor (EDRF) opened the research field of the later discovered molecule nitric oxide (NO). To date, more than 71,000 papers have been published with NO in the title, and more than 260,000 refer to it in some way.

In medicinal chemistry, NO is a very important molecule, since it is involved in several diseases, and many efforts have been made to understand its cellular biosynthesis details and roles. Considering the numerous and continuous achievements over the years, the identification of NO modulators, both synthetic or naturally occurring, represents an attractive and valuable tool for the development of potential new therapeutic agents, useful to preserve health state or control different disease progression.

This Special Issue aims to focus its attention on the most recent advances in the design and synthesis of small molecules, as well as on the discovery of naturally occurring compounds, able to modulate NO bioavailability, and useful as potential therapeutics or nutraceuticals. 

This Special Issue will accept original research papers and high-quality reviews in the field of NO donors, as well as of NO biosynthesis inhibitors and activators, with particular regard to:

  • Their design, synthesis, and structure–activity relationship study;
  • Their isolation and identification from natural sources;
  • Their evaluation as protective and therapeutic agents.

Dr. Cristina Maccallini
Dr. Rosa Amoroso
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. 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

  • activators
  • inhibitors
  • nitric oxide donors
  • nitric oxide synthases
  • nitrosative stress
  • nutraceuticals
  • synthesis
  • structure–activity relationships
  • therapeutics

Related Special Issue

Published Papers (4 papers)

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Research

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17 pages, 2421 KiB  
Article
Investigation of NO Role in Neural Tissue in Brain and Spinal Cord Injury
by Viacheslav V. Andrianov, Vladimir A. Kulchitsky, Guzel G. Yafarova, Leah V. Bazan, Tatiana K. Bogodvid, Irina B. Deryabina, Lyudmila N. Muranova, Dinara I. Silantyeva, Almaz I. Arslanov, Mikhail N. Paveliev, Ekaterina V. Fedorova, Tatiana A. Filipovich, Aleksei V. Nagibov and Khalil L. Gainutdinov
Molecules 2023, 28(21), 7359; https://doi.org/10.3390/molecules28217359 - 31 Oct 2023
Viewed by 863
Abstract
Nitric oxide (NO) production in injured and intact brain regions was compared by EPR spectroscopy in a model of brain and spinal cord injury in Wistar rats. The precentral gyrus of the brain was injured, followed by the spinal cord at the level [...] Read more.
Nitric oxide (NO) production in injured and intact brain regions was compared by EPR spectroscopy in a model of brain and spinal cord injury in Wistar rats. The precentral gyrus of the brain was injured, followed by the spinal cord at the level of the first lumbar vertebra. Seven days after brain injury, a reduction in NO content of 84% in injured brain regions and 66% in intact brain regions was found. The difference in NO production in injured and uninjured brain regions persisted 7 days after injury. The copper content in the brain remained unchanged one week after modeling of brain and spinal cord injury. The data obtained in the experiments help to explain the problems in the therapy of patients with combined brain injury. Full article
(This article belongs to the Special Issue Nitric Oxide Modulators in Health and Disease II)
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16 pages, 3090 KiB  
Article
Design, Synthesis, and Investigation of Novel Nitric Oxide (NO)-Releasing Aromatic Aldehydes as Drug Candidates for the Treatment of Sickle Cell Disease
by Boshi Huang, Mohini S. Ghatge, Akua K. Donkor, Faik N. Musayev, Tanvi M. Deshpande, Mohammed Al-Awadh, Rana T. Alhashimi, Hongmei Zhu, Abdelsattar M. Omar, Marilyn J. Telen, Yan Zhang, Tim J. McMahon, Osheiza Abdulmalik and Martin K. Safo
Molecules 2022, 27(20), 6835; https://doi.org/10.3390/molecules27206835 - 12 Oct 2022
Cited by 3 | Viewed by 1810
Abstract
Sickle cell disease (SCD) is caused by a single-point mutation, and the ensuing deoxygenation-induced polymerization of sickle hemoglobin (HbS), and reduction in bioavailability of vascular nitric oxide (NO), contribute to the pathogenesis of the disease. In a proof-of-concept study, we successfully incorporated nitrate [...] Read more.
Sickle cell disease (SCD) is caused by a single-point mutation, and the ensuing deoxygenation-induced polymerization of sickle hemoglobin (HbS), and reduction in bioavailability of vascular nitric oxide (NO), contribute to the pathogenesis of the disease. In a proof-of-concept study, we successfully incorporated nitrate ester groups onto two previously studied potent antisickling aromatic aldehydes, TD7 and VZHE039, to form TD7-NO and VZHE039-NO hybrids, respectively. These compounds are stable in buffer but demonstrated the expected release of NO in whole blood in vitro and in mice. The more promising VZHE039-NO retained the functional and antisickling activities of the parent VZHE039 molecule. Moreover, VZHE039-NO, unlike VZHE039, significantly attenuated RBC adhesion to laminin, suggesting this compound has potential in vivo RBC anti-adhesion properties relevant to vaso-occlusive events. Crystallographic studies show that, as with VZHE039, VZHE039-NO also binds to liganded Hb to make similar protein interactions. The knowledge gained during these investigations provides a unique opportunity to generate a superior candidate drug in SCD with enhanced benefits. Full article
(This article belongs to the Special Issue Nitric Oxide Modulators in Health and Disease II)
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Review

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14 pages, 890 KiB  
Review
Nitric Oxide (NO) Synthase Inhibitors: Potential Candidates for the Treatment of Anxiety Disorders?
by Nikolaos Pitsikas
Molecules 2024, 29(6), 1411; https://doi.org/10.3390/molecules29061411 - 21 Mar 2024
Viewed by 558
Abstract
Close to 19% of the world population suffers from anxiety. Current medications for this chronic mental disorder have improved treatment over the last half century or more, but the newer anxiolytics have proved disappointing, and enormous challenges remain. Nitric oxide (NO), an intra- [...] Read more.
Close to 19% of the world population suffers from anxiety. Current medications for this chronic mental disorder have improved treatment over the last half century or more, but the newer anxiolytics have proved disappointing, and enormous challenges remain. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, is involved in the pathogenesis of anxiety. In particular, excessive NO production might contribute to its pathology. This implies that it might be useful to reduce nitrergic activity; therefore, molecules aiming to downregulate NO production such as NO synthase inhibitors (NOSIs) might be candidates. Here, it was intended to critically review advances in research on these emerging molecules for the treatment of anxiety disorders. Current assessment indicates that, although NOSIs are implicated in anxiety, their potential anti-anxiety action remains to be established. Full article
(This article belongs to the Special Issue Nitric Oxide Modulators in Health and Disease II)
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18 pages, 1979 KiB  
Review
Involvement of Nitric Oxide in Protecting against Radical Species and Autoregulation of M1-Polarized Macrophages through Metabolic Remodeling
by Junichi Fujii and Tsukasa Osaki
Molecules 2023, 28(2), 814; https://doi.org/10.3390/molecules28020814 - 13 Jan 2023
Cited by 6 | Viewed by 2728
Abstract
When the expression of NOS2 in M1-polarized macrophages is induced, huge amounts of nitric oxide (•NO) are produced from arginine and molecular oxygen as the substrates. While anti-microbial action is the primary function of M1 macrophages, excessive activation may result in inflammation being [...] Read more.
When the expression of NOS2 in M1-polarized macrophages is induced, huge amounts of nitric oxide (•NO) are produced from arginine and molecular oxygen as the substrates. While anti-microbial action is the primary function of M1 macrophages, excessive activation may result in inflammation being aggravated. The reaction of •NO with superoxide produces peroxynitrite, which is highly toxic to cells. Alternatively, however, this reaction eliminates radial electrons and may occasionally alleviate subsequent radical-mediated damage. Reactions of •NO with lipid radicals terminates the radical chain reaction in lipid peroxidation, which leads to the suppression of ferroptosis. •NO is involved in the metabolic remodeling of M1 macrophages. Enzymes in the tricarboxylic acid (TCA) cycle, notably aconitase 2, as well as respiratory chain enzymes, are preferential targets of •NO derivatives. Ornithine, an alternate compound produced from arginine instead of citrulline and •NO, is recruited to synthesize polyamines. Itaconate, which is produced from the remodeled TCA cycle, and polyamines function as defense systems against overresponses of M1 macrophages in a feedback manner. Herein, we overview the protective aspects of •NO against radical species and the autoregulatory systems that are enabled by metabolic remodeling in M9-polarized macrophages. Full article
(This article belongs to the Special Issue Nitric Oxide Modulators in Health and Disease II)
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