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Special Issue "Protease and Carbonic Anhydrase Inhibitors, II"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 September 2019

Special Issue Editor

Guest Editor
Prof. Dr. Claudiu T. Supuran

Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino (Florence) 50019, Italy
Website | E-Mail
Fax: +39-055-4573385
Interests: drug design; metalloenzymes; carbonic anhydrases, anticancer agents; antiinfectives; sulfonamides; coumarins

Special Issue Information

Dear Colleagues,

Proteases and carbonic anhydrases are among the most widespread enzymes in organisms all over the phylogenetic tree, in which they play crucial physiological roles. Dysregulation of their activity is connected with many diseases, such as tumors, viral infections, blood coagulation disorders, digestive diseases, etc. Protease inhibitors targeting all classes of such known enzymes are widely used as antivirals (against HIV and hepatitis C infections), antithromodotics (targeting serine proteases involved in the blood coagulation cascade), whereas inhibitors of other proteases, such as matrix metalloproteinases, have found fewer applications due to their toxicity problems. Carbonic anhydrase inhibitors, on the other hand, are used as antiglaucoma, antiepileptic, antiobesity, and as diuretic drugs, whereas newer applications target metastatic tumors, both for treatment and imaging, with one small molecule and one antibody in advanced clinical trials. Antiinfectives, based on inhibition of carbonic anhydrases from pathogenic bacteria, fungi, and protozoa, have also begun to be investigated.

The present Special Issue of the International Journal of Molecular Sciences welcomes contributions dealing with all aspects connected to the chemistry, biochemistry, pharmacology and toxicology of this important class of enzyme inhibitors.

You may wish to check the previous volume.

Prof. Dr. Claudiu T. Supuran
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 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. 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. The Article Processing Charge (APC) for publication in this open access journal is 1800 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

  • carbonic anhydrase
  • protease
  • inhibitor
  • antiviral drug
  • antitumor drug
  • drug design
  • serine protease
  • metalloprotease
  • aspartic protease

Published Papers (2 papers)

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Research

Open AccessArticle
Indole-Based Hydrazones Containing A Sulfonamide Moiety as Selective Inhibitors of Tumor-Associated Human Carbonic Anhydrase Isoforms IX and XII
Int. J. Mol. Sci. 2019, 20(9), 2354; https://doi.org/10.3390/ijms20092354
Received: 1 April 2019 / Revised: 23 April 2019 / Accepted: 10 May 2019 / Published: 12 May 2019
PDF Full-text (1707 KB) | HTML Full-text | XML Full-text
Abstract
Novel sulfonamidoindole-based hydrazones with a 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide scaffold were synthesized and tested in enzyme inhibition assays against the tumor-associated carbonic anhydrase isoforms, hCA IX and XII, and the off-targets, hCA I and II. The compounds showed selectivity against hCA IX and XII [...] Read more.
Novel sulfonamidoindole-based hydrazones with a 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide scaffold were synthesized and tested in enzyme inhibition assays against the tumor-associated carbonic anhydrase isoforms, hCA IX and XII, and the off-targets, hCA I and II. The compounds showed selectivity against hCA IX and XII over hCA I and II. Six compounds showed KI values lower than 10 nM against hCA IX or XII. Molecular modeling studies were performed to suggest binding interactions between the ligand and the hCA active sites. Full article
(This article belongs to the Special Issue Protease and Carbonic Anhydrase Inhibitors, II)
Figures

Graphical abstract

Open AccessArticle
Novel 8-Substituted Coumarins That Selectively Inhibit Human Carbonic Anhydrase IX and XII
Int. J. Mol. Sci. 2019, 20(5), 1208; https://doi.org/10.3390/ijms20051208
Received: 15 February 2019 / Revised: 4 March 2019 / Accepted: 6 March 2019 / Published: 10 March 2019
PDF Full-text (1892 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel series of 8-substituted coumarin-based compounds, characterized by the presence of alkylpiperazine and arylpiperazine chains, were synthesized and tested for their inhibitory activity against four human carbonic anhydrase (hCA) isoforms. All compounds displayed nanomolar potency against the cancer-related hCA [...] Read more.
A novel series of 8-substituted coumarin-based compounds, characterized by the presence of alkylpiperazine and arylpiperazine chains, were synthesized and tested for their inhibitory activity against four human carbonic anhydrase (hCA) isoforms. All compounds displayed nanomolar potency against the cancer-related hCA IX and hCA XII; moreover, they were shown to be devoid of any inhibitory activity toward the cytosolic hCA I and hCA II up to 10 µM concentration in the assay system. Therefore, the synthesized coumarin ligands demonstrated to be potent and selective hCA IX/XII inhibitors, and were shown to be as potent as the reference inhibitor acetazolamide against hCA XII, with single-digit nanomolar Ki values. Molecular modeling studies provided a rationale for explaining the selectivity profile of these non-classic hCA inhibitors and their interactions with the enzymes, according to their specific mechanism of action, thus paving the way for future structure-based lead optimization studies. Full article
(This article belongs to the Special Issue Protease and Carbonic Anhydrase Inhibitors, II)
Figures

Figure 1

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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