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Synthesis and Transformations of Bioactive Hydroxyquinolines

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 12133

Special Issue Editor


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Guest Editor
Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Hungary
Interests: indole derivatives; 8-hydroxyquinolines; 4-hydroxyquinoline-2-carboxylic acid (KYNA) derivatives; β-carbolines; drug design and synthesis; ortho-quinone methides; modified Mannich reaction; modified aza-Friedel–Crafts reaction
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Special Issue Information

Dear Colleagues,

We are delighted to announce a call for submissions to a Special Issue of the International Journal of Molecular Sciences on the topic of “Synthesis and Transformations of Bioactive Hydroxyquinolines”.

Privileged structures can bind to a diverse range of targets with high affinities, thus benefitting the discovery of novel bioactive agents. Hydroxyquinoline derivatives represent an important type of such a privileged structure, possessing a rich diversity of biological properties.

One participant of such compounds is 4-hydroxyquinoline-2-carboxylic acid (kynurenic acid or KYNA). It is one of the few endogenous excitatory amino acid receptor blockers, produced via the metabolism of tryptophan (TRP). It is well established that KYNA has high affinity toward NMDA receptors and a high affinity toward positive modulatory binding sites at the AMPA receptor that are assumed to be the reasons for its biological effects.

On the other hand, 8-hydroxyquinoline itself or its derivatives have a broad pharmacological activity and have been exploited in several medicinal applications ranging from anti-neurodegenerative, anti-inflammatory, and antimicrobial to anticancer therapies.

We encourage the submission of both original research articles and topical reviews on all aspects of synthesis and pharmacological studies on hydroxyquinoline derivatives. All submitted articles will undergo peer review.

Prof. Dr. István Szatmári
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • hydroxyquinolines
  • 8-quinolinols
  • 4-hydroxyquinoline-2-carboxylic acid (KYNA)
  • bioactive compounds
  • neuroprotection
  • antiproliferative activity

Published Papers (4 papers)

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Research

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29 pages, 5976 KiB  
Article
8-Hydroxyquinoline-Amino Acid Hybrids and Their Half-Sandwich Rh and Ru Complexes: Synthesis, Anticancer Activities, Solution Chemistry and Interaction with Biomolecules
by Tamás Pivarcsik, Orsolya Dömötör, János P. Mészáros, Nóra V. May, Gabriella Spengler, Oszkár Csuvik, István Szatmári and Éva A. Enyedy
Int. J. Mol. Sci. 2021, 22(20), 11281; https://doi.org/10.3390/ijms222011281 - 19 Oct 2021
Cited by 11 | Viewed by 3709
Abstract
Solution chemical properties of two novel 8-hydroxyquinoline-D-proline and homo-proline hybrids were investigated along with their complex formation with [Rh(η5-C5Me5)(H2O)3]2+ and [Ru(η6-p-cymene)(H2O)3]2+ ions by [...] Read more.
Solution chemical properties of two novel 8-hydroxyquinoline-D-proline and homo-proline hybrids were investigated along with their complex formation with [Rh(η5-C5Me5)(H2O)3]2+ and [Ru(η6-p-cymene)(H2O)3]2+ ions by pH-potentiometry, UV-visible spectrophotometry and 1H NMR spectroscopy. Due to the zwitterionic structure of the ligands, they possess excellent water solubility as well as their complexes. The complexes exhibit high solution stability in a wide pH range; no significant dissociation occurs at physiological pH. The hybrids and their Rh(η5-C5Me5) complexes displayed enhanced cytotoxicity in human colon adenocarcinoma cell lines and exhibited multidrug resistance selectivity. In addition, the Rh(η5-C5Me5) complexes showed increased selectivity to the chemosensitive cancer cells over the normal cells; meanwhile, the Ru(η6-p-cymene) complexes were inactive, most likely due to arene loss. Interaction of the complexes with human serum albumin (HSA) and calf-thymus DNA (ct-DNA) was investigated by capillary electrophoresis, fluorometry and circular dichroism. The complexes are able to bind strongly to HSA and ct-DNA, but DNA cleavage was not observed. Changing the five-membered proline ring to the six-membered homoproline resulted in increased lipophilicity and cytotoxicity of the Rh(η5-C5Me5) complexes while changing the configuration (L vs. D) rather has an impact on HSA or ct-DNA binding. Full article
(This article belongs to the Special Issue Synthesis and Transformations of Bioactive Hydroxyquinolines)
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18 pages, 3292 KiB  
Article
Synthesis of Novel Spiro-Tetrahydroquinoline Derivatives and Evaluation of Their Pharmacological Effects on Wound Healing
by Yan-Cheng Liou, Yan-An Lin, Ke Wang, Juan-Cheng Yang, Yeong-Jiunn Jang, Wenwei Lin and Yang-Chang Wu
Int. J. Mol. Sci. 2021, 22(12), 6251; https://doi.org/10.3390/ijms22126251 - 10 Jun 2021
Cited by 6 | Viewed by 2252
Abstract
A highly diastereoselective method for the synthesis of novel spiro-tetrahydroquinoline derivatives is reported here, using a one-pot reaction method. All compounds were characterized by 1H-nuclear magnetic resonance (NMR) and mass spectroscopy, and their stereo configurations were confirmed by X-ray analysis. These [...] Read more.
A highly diastereoselective method for the synthesis of novel spiro-tetrahydroquinoline derivatives is reported here, using a one-pot reaction method. All compounds were characterized by 1H-nuclear magnetic resonance (NMR) and mass spectroscopy, and their stereo configurations were confirmed by X-ray analysis. These activities of these derivatives were then tested in human keratocyte cells. The responses of cells to treatment with selected compounds were studied using scratch analysis, and the compounds were tested in a mouse excision wound model. Three of the derivatives demonstrated significant wound-healing activities. Full article
(This article belongs to the Special Issue Synthesis and Transformations of Bioactive Hydroxyquinolines)
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Review

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24 pages, 5436 KiB  
Review
KYNA Derivatives with Modified Skeleton; Hydroxyquinolines with Potential Neuroprotective Effect
by Bálint Lőrinczi and István Szatmári
Int. J. Mol. Sci. 2021, 22(21), 11935; https://doi.org/10.3390/ijms222111935 - 3 Nov 2021
Cited by 4 | Viewed by 2013
Abstract
Kynurenic acid (KYNA) is an endogenous neuroprotective agent of increasing importance. Several derivatives have already been synthesized, bearing an abundance of functional groups attached to the main skeleton in different positions. Several of these compounds have already been tested in biological evaluations, with [...] Read more.
Kynurenic acid (KYNA) is an endogenous neuroprotective agent of increasing importance. Several derivatives have already been synthesized, bearing an abundance of functional groups attached to the main skeleton in different positions. Several of these compounds have already been tested in biological evaluations, with several of them targeting the same receptors and biological effects as KYNA. However, these modified compounds build upon the unmodified KYNA skeleton leaving a possible route for the synthesis of new, potentially neuroprotective derivatives with heteroatom-containing ring systems. The aim of this review is to summarize the syntheses of KYNA derivatives with altered skeletons and to pinpoint an appealing transformation for future medicinal lead molecules. Full article
(This article belongs to the Special Issue Synthesis and Transformations of Bioactive Hydroxyquinolines)
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18 pages, 1640 KiB  
Review
The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives
by Katarzyna Ciapała, Joanna Mika and Ewelina Rojewska
Int. J. Mol. Sci. 2021, 22(20), 11055; https://doi.org/10.3390/ijms222011055 - 13 Oct 2021
Cited by 27 | Viewed by 3437
Abstract
Accumulating evidence suggests the key role of the kynurenine pathway (KP) of the tryptophan metabolism in the pathogenesis of several diseases. Despite extensive research aimed at clarifying the mechanisms underlying the development and maintenance of neuropathic pain, the roles of KP metabolites in [...] Read more.
Accumulating evidence suggests the key role of the kynurenine pathway (KP) of the tryptophan metabolism in the pathogenesis of several diseases. Despite extensive research aimed at clarifying the mechanisms underlying the development and maintenance of neuropathic pain, the roles of KP metabolites in this process are still not fully known. Although the function of the peripheral KP has been known for several years, it has only recently been acknowledged that its metabolites within the central nervous system have remarkable consequences related to physiology and behavior. Both the products and metabolites of the KP are involved in the pathogenesis of pain conditions. Apart from the neuroactive properties of kynurenines, the KP regulates several neurotransmitter systems in direct or indirect ways. Some neuroactive metabolites are known to have neuroprotective properties (kynurenic acid, nicotinamide adenine dinucleotide cofactor), while others are toxic (3-hydroxykynurenine, quinolinic acid). Numerous animal models show that modulation of the KP may turn out to be a viable target for the treatment of diseases. Importantly, some compounds that affect KP enzymes are currently described to possess analgesic properties. Additionally, kynurenine metabolites may be useful for assessing response to therapy or as biomarkers in therapeutic monitoring. The following review describes the molecular site of action and changes in the levels of metabolites of the kynurenine pathway in the pathogenesis of various conditions, with a particular emphasis on their involvement in neuropathy. Moreover, the potential clinical implications of KP modulation in chronic pain therapy as well as the directions of new research initiatives are discussed. Full article
(This article belongs to the Special Issue Synthesis and Transformations of Bioactive Hydroxyquinolines)
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