Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0

Special Issue Editors
Special Issue Information
Keywords
Published Papers

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

Deadline for manuscript submissions: 30 June 2024 | Viewed by 11322

Share This Special Issue

Special Issue Editor

Prof. Dr. Athina Geronikaki

E-Mail Website
Guest Editor

School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece
Interests: biologically active heterocycles; thiazole; thiazolidinone; benzothiazole; thiadiazoles with antimicrobial activity; COX/LOX, PTP1b, HIV RT enzyme inhibitors; anti inflammatory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue aims to gather research and review articles on enzymes and enzyme inhibitors with applications in diagnosis and therapy, covering a vast area of medical research.

As enzymes are involved in all biochemical processes, there are numerous pathological disorders related to the deficiency, malfunction, reduced/increased activity or overexpression of enzymes. In addition, deficiencies of enzyme inhibitors are also responsible for serious diseases. Therefore, the study of enzymes and their inhibitors is crucial for the elucidation of the pathophysiology of diseases and the exploration of therapeutic strategies, representing a great area of continuous research.

The role of enzymes in the regulation of all processes has turned them into important drug targets. Enzyme inhibitors constitute the second-greatest drug category, following receptor agonists and antagonists. Enzyme inhibitors are among the drugs used for the treatment of metabolic and degenerative diseases, including hypercholesterolemia, diabetes and hypertension, as well as antimicrobial and antiviral therapy. The large number of isoenzymes necessitates the development of highly specific and effective inhibitors in order to achieve target effects with fewer undesired side effects. This goal leads to the continuation of research for the development of novel and improved inhibitors, even for old enzyme targets, while the development of resistant strains in antimicrobial and antiviral therapy underlines the continuous need for novel inhibitors and novel targets.

In the field of diagnosis, enzymes constitute important biomolecules. The levels of several enzymes and specific isoenzymes are measured for the diagnosis and monitoring of diseases. Although specific isoenzyme inhibitors enable the differential measurement of organ-specific isoenzymes in some cases, such effective inhibitors have not been found for most of the enzymes. On the other hand, the number of enzymes and related methods being used in enzymatic assays for the measurement of other biomarkers in classic methods, dry chemistry and bioelectrode-based techniques is increasing.

We call on you to contribute to this Special Issue by submitting your research as well as review articles in the field.

Prof. Dr. Athina Geronikaki
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

enzyme
enzyme inhibitor
drug target
enzyme deficiency
enzyme overexpression
biomarker
drugs
diagnosis
therapy

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review, Other

31 pages, 9503 KiB

Open AccessArticle

Silver and Gold Complexes with NHC-Ligands Derived from Caffeine: Catalytic and Pharmacological Activity

by Annaluisa Mariconda, Domenico Iacopetta, Marco Sirignano, Jessica Ceramella, Assunta D’Amato, Maria Marra, Michele Pellegrino, Maria Stefania Sinicropi, Stefano Aquaro and Pasquale Longo

Int. J. Mol. Sci. 2024, 25(5), 2599; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25052599 - 23 Feb 2024

Viewed by 682

Abstract

N-heterocyclic carbene (NHC) silver(I) and gold(I) complexes have found different applications in various research fields, as in medicinal chemistry for their antiproliferative, anticancer, and antibacterial activity, and in chemistry as innovative and effective catalysts. The possibility of modulating the physicochemical properties, by acting on their ligands and substituents, makes them versatile tools for the development of novel metal-based compounds, mostly as anticancer compounds. As it is known, chemotherapy is commonly adopted for the clinical treatment of different cancers, even though its efficacy is hampered by several factors. Thus, the development of more effective and less toxic drugs is still an urgent need. Herein, we reported the synthesis and characterization of new silver(I) and gold(I) complexes stabilized by caffeine-derived NHC ligands, together with their biological and catalytic activities. Our data highlight the interesting properties of this series as effective catalysts in A³-coupling and hydroamination reactions and as promising anticancer, anti-inflammatory, and antioxidant agents. The ability of these complexes in regulating different pathological aspects, and often co-promoting causes, of cancer makes them ideal leads to be further structurally functionalized and investigated. Full article

(This article belongs to the Special Issue Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0)

► Show Figures

Figure 1

15 pages, 3042 KiB

Open AccessArticle

Altered Serum Alpha1-Antitrypsin Protease Inhibition before and after Clinical Hematopoietic Stem Cell Transplantation: Association with Risk for Non-Relapse Mortality

by Ido Brami, Tsila Zuckerman, Ron Ram, Batia Avni, Galit Peretz, Daniel Ostrovsky, Yotam Lior, Caroline Faour, Oisin McElvaney, Noel G. McElvaney and Eli C. Lewis

Int. J. Mol. Sci. 2024, 25(1), 422; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25010422 - 28 Dec 2023

Viewed by 892

Abstract

α1-Antitrypsin (AAT), an acute-phase reactant not unsimilar to C-reactive protein (CRP), is a serine protease inhibitor that harbors tissue-protective and immunomodulatory attributes. Its concentrations appropriately increase during conditions of extensive tissue injury, and it induces immune tolerance, in part, by inhibiting the enzymatic activity of the inflammatory serine protease, proteinase 3 (PR3). Typically administered to patients with genetic AAT deficiency, AAT treatment was recently shown to improve outcomes in patients with steroid-refractory graft-versus-host disease (GVHD). GVHD represents a grave outcome of allogeneic hematopoietic stem cell transplantation (HSCT), a potentially curative intervention for hematological diseases. The procedure requires radio/chemotherapy conditioning of the prospective marrow recipient, a cytotoxic process that causes vast tissue injury and, in some formats, interferes with liver production of AAT. To date, changes in the functional profile of AAT during allogeneic HSCT, and during the cytotoxic intervention that precedes HSCT, are unknown. The present study followed 53 patients scheduled for allogeneic HSCT (trial registration NCT03188601). Serum samples were tested before and after HSCT for AAT and CRP levels and for intrinsic anti-proteolytic activity. The ex vivo response to clinical-grade AAT was tested on circulating patient leukocytes and on a human epithelial cell line treated with patient sera in a gap closure assay. According to the ex vivo experiments, circulating leukocytes responded to AAT with a favorable immune-regulated profile, and epithelial gap closure was enhanced by AAT in sera from GVHD-free patients but not in sera from patients who developed GVHD. According to serum collected prior to HSCT, non-relapse mortality was reliably predicted by combining three components: AAT and CRP levels and serum anti-proteolytic activity. Taken together, HSCT outcomes are significantly affected by the anti-proteolytic function of circulating AAT, supporting early AAT augmentation therapy for allogeneic HSCT patients. Full article

(This article belongs to the Special Issue Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0)

► Show Figures

Figure 1

21 pages, 7518 KiB

Open AccessArticle

Chemical and Biological Evaluation of Novel 1H-Chromeno[3,2-c]pyridine Derivatives as MAO Inhibitors Endowed with Potential Anticancer Activity

by Larisa N. Kulikova, Rosa Purgatorio, Andrey A. Beloglazkin, Viktor A. Tafeenko, Raesi Gh. Reza, Daria D. Levickaya, Sabina Sblano, Angelina Boccarelli, Modesto de Candia, Marco Catto, Leonid G. Voskressensky and Cosimo D. Altomare

Int. J. Mol. Sci. 2023, 24(9), 7724; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24097724 - 23 Apr 2023

Cited by 1 | Viewed by 1484

Abstract

About twenty molecules sharing 1H-chromeno[3,2-c]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl at C1 and 1H-indol-3-yl fragments at C10, as well as a few small substituents at C6 and C8, were synthesized starting from 1,2,3,4-tetrahydro-2-methylchromeno[3,2-c]pyridin-10-ones (1,2,3,4-THCP-10-ones, 1) or 2,3-dihydro-2-methyl-1H-chromeno[3,2-c]pyridines (2,3-DHPCs, 2). The newly synthesized compounds were tested as inhibitors of the human isoforms of monoamine oxidase (MAO A and B) and cholinesterase (AChE and BChE), and the following main SARs were inferred: (i) The 2,3-DHCP derivatives 2 inhibit MAO A (IC₅₀ about 1 μM) preferentially; (ii) the 1,2,3,4-THCP-10-one 3a, bearing the phenylethynyl fragment at C1, returned as a potent MAO B inhibitor (IC₅₀ 0.51 μM) and moderate inhibitor of both ChEs (IC₅₀s 7–8 μM); (iii) the 1H-indol-3-yl fragment at C10 slightly increases the MAO B inhibition potency, with the analog 6c achieving MAO B IC₅₀ of 3.51 μM. The MAO B inhibitor 3a deserves further pharmacological studies as a remedy in the symptomatic treatment of Parkinson’s disease and neuroprotectant for Alzheimer’s disease. Besides the established neuroprotective effects of MAO inhibitors, the role of MAOs in tumor insurgence and progression has been recently reported. Herein, antiproliferative assays with breast (MCF-7), colon (HCT116) and cisplatin-resistant ovarian (SK-OV-3) tumor cells revealed that the 10-indolyl-bearing 2,3,4,10-THCP analog 6c exerts anti-tumor activity with IC₅₀s in the range 4.83–11.3 μM. Full article

(This article belongs to the Special Issue Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0)

► Show Figures

Graphical abstract

25 pages, 6284 KiB

Open AccessArticle

Targeting of the Mitochondrial TET1 Protein by Pyrrolo[3,2-b]pyrrole Chelators

by Veronika Antonyová, Ameneh Tatar, Tereza Brogyányi, Zdeněk Kejík, Robert Kaplánek, Fréderic Vellieux, Nikita Abramenko, Alla Sinica, Jan Hajduch, Petr Novotný, Bettie Sue Masters, Pavel Martásek and Milan Jakubek

Int. J. Mol. Sci. 2022, 23(18), 10850; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810850 - 16 Sep 2022

Cited by 3 | Viewed by 1877

Abstract

Targeting of epigenetic mechanisms, such as the hydroxymethylation of DNA, has been intensively studied, with respect to the treatment of many serious pathologies, including oncological disorders. Recent studies demonstrated that promising therapeutic strategies could potentially be based on the inhibition of the TET1 protein (ten-eleven translocation methylcytosine dioxygenase 1) by specific iron chelators. Therefore, in the present work, we prepared a series of pyrrolopyrrole derivatives with hydrazide (1) or hydrazone (2–6) iron-binding groups. As a result, we determined that the basic pyrrolo[3,2-b]pyrrole derivative 1 was a strong inhibitor of the TET1 protein (IC₅₀ = 1.33 μM), supported by microscale thermophoresis and molecular docking. Pyrrolo[3,2-b]pyrroles 2–6, bearing substituted 2-hydroxybenzylidene moieties, displayed no significant inhibitory activity. In addition, in vitro studies demonstrated that derivative 1 exhibits potent anticancer activity and an exclusive mitochondrial localization, confirmed by Pearson’s correlation coefficient of 0.92. Full article

(This article belongs to the Special Issue Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0)

► Show Figures

Graphical abstract

Review

Jump to: Research, Other

20 pages, 5101 KiB

Open AccessReview

PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes

by Jian Jin, Francesca Mazzacuva, Letizia Crocetti, Maria Paola Giovannoni and Agostino Cilibrizzi

Int. J. Mol. Sci. 2023, 24(14), 11518; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241411518 - 15 Jul 2023

Cited by 1 | Viewed by 2215

Abstract

Cyclic nucleotide phosphodiesterases 4 (PDE4) are a family of enzymes which specifically promote the hydrolysis and degradation of cAMP. The inhibition of PDE4 enzymes has been widely investigated as a possible alternative strategy for the treatment of a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma, as well as psoriasis and other autoimmune disorders. In this context, the identification of new molecules as PDE4 inhibitors continues to be an active field of investigation within drug discovery. This review summarizes the medicinal chemistry journey in the design and development of effective PDE4 inhibitors, analyzed through chemical classes and taking into consideration structural aspects and binding properties, as well as inhibitory efficacy, PDE4 selectivity and the potential as therapeutic agents. Full article

(This article belongs to the Special Issue Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0)

► Show Figures

Figure 1

Other

Jump to: Research, Review

10 pages, 964 KiB

Open AccessCommentary

Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies

by Kostas A. Papavassiliou, Vassiliki A. Gogou and Athanasios G. Papavassiliou

Int. J. Mol. Sci. 2023, 24(24), 17441; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242417441 - 13 Dec 2023

Viewed by 896

Abstract

Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by excessive pulmonary vasoconstriction and abnormal vascular remodeling processes that lead to right-ventricular heart failure and, ultimately, death. Although our understanding of its pathophysiology has advanced and several treatment modalities are currently available for the management of PAH patients, none are curative and the prognosis remains poor. Therefore, further research is required to decipher the molecular mechanisms associated with PAH. Angiotensin-converting enzyme 2 (ACE2) plays an important role through its vasoprotective functions in cardiopulmonary homeostasis, and accumulating preclinical and clinical evidence shows that the upregulation of the ACE2/Angiotensin-(1-7)/MAS1 proto-oncogene, G protein-coupled receptor (Mas 1 receptor) signaling axis is implicated in the pathophysiology of PAH. Herein, we highlight the molecular mechanisms of ACE2 signaling in PAH and discuss its potential as a therapeutic target. Full article

(This article belongs to the Special Issue Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0)

► Show Figures

Figure 1

9 pages, 625 KiB

Open AccessOpinion

Recent Developments in the Inhibition of Bacterial Adhesion as Promising Anti-Virulence Strategy

by Camilla Pecoraro, Daniela Carbone, Barbara Parrino, Stella Cascioferro and Patrizia Diana

Int. J. Mol. Sci. 2023, 24(5), 4872; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054872 - 02 Mar 2023

Cited by 13 | Viewed by 1711

Abstract

Infectious diseases caused by antimicrobial-resistant strains have become a serious threat to global health, with a high social and economic impact. Multi-resistant bacteria exhibit various mechanisms at both the cellular and microbial community levels. Among the different strategies proposed to fight antibiotic resistance, we reckon that the inhibition of bacterial adhesion to host surfaces represents one of the most valid approaches, since it hampers bacterial virulence without affecting cell viability. Many different structures and biomolecules involved in the adhesion of Gram-positive and Gram-negative pathogens can be considered valuable targets for the development of promising tools to enrich our arsenal against pathogens. Full article

(This article belongs to the Special Issue Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (7 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI