Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ)

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: 20 May 2024 | Viewed by 12597

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Departamento de Química e Bioquímica (DQB) e Centro de Química e Bioquímica (CQB), Faculdade de Ciências, Universidade de Lisboa (FCUL), Rua Ernesto de Vasconcelos, Campo Grande,Edifício C8, 5º Piso, 1749-016 Lisboa, Portugal
Interests: carbohydrate small molecule synthesis; organic and biomolecular chemistry developments towards new therapeutic approaches for diabetes; Alzheimer’s disease and other amyloid diseases and carbohydrate-based antibiotics
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Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, 01328 Dresden, Germany
Interests: radiopharmaceutical drug development; radiopharmaceutical sciences; medicinal radiochemistry; radionuclide theranostics; targeted endoradiotherapy; noninvasive molecular imaging; PET; SPECT
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Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany
Interests: natural products; molecular pharmacology; cancer; drug resistance; genome-wide profiling
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PharmaCampus Institute of Pharmaceutical and Medicinal Chemistry, Westfälische Wilhelms-Universität, Corrensstr. 48, 48149 Muenster, Germany
Interests: autodisplay; assay development and inhibitor testing; whole cell biocatalysts for synthesis of drugs and building blocks; directed evolution of enzyme inhibitors and biocatalysts; biosensor development and diagnostic tools
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1. Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), 4450-208 Porto, Portugal
2. Laboratory of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Interests: medicinal chemistry; organic synthesis; heterocycles; P-glycoprotein; anticancer; antimicrobials; chiral drugs; marine natural products
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Special Issue Information

Dear Colleagues,

Dr. Jean Jacques Vanden Eynde has been the Editor-in-Chief Pharmaceuticals from 2015 to 2022. Being an organic chemist, his vision and his important contributions to the success of the journal, including fostering a friendly atmosphere between the journal and Section Editors, have indeed been highly appreciated. With enthusiasm that can be recognized by all of us, this great scientist and great Editor-in-Chief has promoted the publication of many original and review articles as well as Special Issues covering relevant topics in the scientific community, especially in the field pharmaceutical sciences, in addition to always being kind, wise, and open-minded. He introduced the Electronic Conference on Medicinal Chemistry, the ECMC, long before the pandemic, and this event is taking place for the eighth time this year, truly representing a great success. It is for us a privilege to honor him with a Special Issue dedicated to the most recent advances in pharmaceutical sciences. Original papers and reviews on topics covered by the journal Pharmaceuticals and by each of its sections are welcome.

Prof. Dr. Amélia Pilar Rauter
Prof. Dr. Klaus Kopka
Prof. Dr. Thomas Efferth
Prof. Dr. Joachim Jose
Prof. Dr. Maria Emília De Sousa
Prof. Dr. Guangshun Wang
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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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

  • medicinal chemistry
  • biopharmaceuticals
  • natural products
  • radiopharmaceutical sciences
  • pharmacology and pharmaceutical technology

Published Papers (8 papers)

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Research

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13 pages, 2624 KiB  
Article
Solidagenone from Solidago chilensis Meyen Protects against Acute Peritonitis and Lipopolysaccharide-Induced Shock by Regulating NF-κB Signaling Pathway
by Ivanilson Pimenta Santos, Laís Peres Silva, Dahara Keyse Carvalho Silva, Bruna Padilha Zurita Claro dos Reis, Temistocles Barroso de Oliveira, Andressa Maia Kelly, Edivaldo dos Santos Rodrigues, Claudia Valeria Campos de Souza, José Fernando Oliveira-Costa, Simone Sacramento Valverde, Osvaldo Andrade Santos-Filho, Milena Botelho Pereira Soares and Cássio Santana Meira
Pharmaceuticals 2024, 17(3), 273; https://doi.org/10.3390/ph17030273 - 21 Feb 2024
Viewed by 847
Abstract
Anti-inflammatory agents are widely used for the treatment of inflammatory diseases. Nevertheless, the associated side effects of the available drugs make it necessary to search for new anti-inflammatory drugs. Here, we investigated the anti-inflammatory activity of solidagenone. Initially, we observed that a single [...] Read more.
Anti-inflammatory agents are widely used for the treatment of inflammatory diseases. Nevertheless, the associated side effects of the available drugs make it necessary to search for new anti-inflammatory drugs. Here, we investigated the anti-inflammatory activity of solidagenone. Initially, we observed that a single dose of 30, 60, or 90 mg/kg of solidagenone did not result in mortality or elicit any discernible signs of toxicity in mice. At the same doses, solidagenone promoted a significant reduction in the migration of neutrophils in an acute peritonitis model and decreased mortality in a lipopolysaccharide-induced endotoxic shock model. Interestingly, treatment with solidagenone conferred a protective effect against leukopenia and thrombocytopenia, hematological disorders commonly observed in sepsis conditions. In addition, treatment with all the doses of solidagenone promoted a significant reduction in nitric oxide, TNF-α, and IL-1β levels relative to the LPS-stimulated vehicle-treated cultures. Furthermore, gene expression and in silico analyses also supported the modulation of the NF-κB pathway by solidagenone. Finally, in silico pharmacokinetics predictions indicated a favorable drugability profile for solidagenone. Taken together, the findings of the present investigation show that solidagenone exhibits significant anti-inflammatory properties in acute experimental models, potentially through the modulation of the NF-κB signaling pathway. Full article
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17 pages, 5445 KiB  
Article
Assessing Nasal Epithelial Dynamics: Impact of the Natural Nasal Cycle on Intranasal Spray Deposition
by Amr Seifelnasr, Xiuhua Si and Jinxiang Xi
Pharmaceuticals 2024, 17(1), 73; https://doi.org/10.3390/ph17010073 - 06 Jan 2024
Viewed by 1023
Abstract
This study investigated the intricate dynamics of intranasal spray deposition within nasal models, considering variations in head orientation and stages of the nasal cycle. Employing controlled delivery conditions, we compared the deposition patterns of saline nasal sprays in models representing congestion (N1), normal [...] Read more.
This study investigated the intricate dynamics of intranasal spray deposition within nasal models, considering variations in head orientation and stages of the nasal cycle. Employing controlled delivery conditions, we compared the deposition patterns of saline nasal sprays in models representing congestion (N1), normal (N0), and decongestion (P1, P2) during one nasal cycle. The results highlighted the impact of the nasal cycle on spray distribution, with congestion leading to confined deposition and decongestion allowing for broader dispersion of spray droplets and increased sedimentation towards the posterior turbinate. In particular, the progressive nasal dilation from N1 to P2 decreased the spray deposition in the middle turbinate. The head angle, in conjunction with the nasal cycle, significantly influenced the nasal spray deposition distribution, affecting targeted drug delivery within the nasal cavity. Despite controlled parameters, a notable variance in deposition was observed, emphasizing the complex interplay of gravity, flow shear, nasal cycle, and nasal morphology. The magnitude of variance increased as the head tilt angle increased backward from upright to 22.5° to 45° due to increasing gravity and liquid film destabilization, especially under decongestion conditions (P1, P2). This study’s findings underscore the importance of considering both natural physiological variations and head orientation in optimizing intranasal drug delivery. Full article
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26 pages, 10761 KiB  
Article
Styrylpyridinium Derivatives for Fluorescent Cell Imaging
by Reinis Putralis, Ksenija Korotkaja, Martins Kaukulis, Zhanna Rudevica, Juris Jansons, Olga Nilova, Martins Rucins, Laura Krasnova, Ilona Domracheva, Mara Plotniece, Karlis Pajuste, Arkadij Sobolev, Felikss Rumnieks, Laura Bekere, Anna Zajakina, Aiva Plotniece and Gunars Duburs
Pharmaceuticals 2023, 16(9), 1245; https://doi.org/10.3390/ph16091245 - 04 Sep 2023
Viewed by 907
Abstract
A set of styrylpyridinium (SP) compounds was synthesised in order to study their spectroscopic and cell labelling properties. The compounds comprised different electron donating parts (julolidine, p-dimethylaminophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyl), conjugated linkers (vinyl, divinyl), and an electron-withdrawing N-alkylpyridinium part. Geminal or [...] Read more.
A set of styrylpyridinium (SP) compounds was synthesised in order to study their spectroscopic and cell labelling properties. The compounds comprised different electron donating parts (julolidine, p-dimethylaminophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyl), conjugated linkers (vinyl, divinyl), and an electron-withdrawing N-alkylpyridinium part. Geminal or bis-compounds incorporating two styrylpyridinium (bis-SP) moieties at the 1,3-trimethylene unit were synthesised. Compounds comprising a divinyl linker and powerful electron-donating julolidine donor parts possessed intensive fluorescence in the near-infrared region (maximum at ~760 nm). The compounds had rather high cytotoxicity towards the cancerous cell lines HT-1080 and MH-22A; at the same time, basal cytotoxicity towards the NIH3T3 fibroblast cell line ranged from toxic to harmful. SP compound 6e had IC50 values of 1.0 ± 0.03 µg/mL to the cell line HT-1080 and 0.4 µg/mL to MH-22A; however, the basal toxicity LD50 was 477 mg/kg (harmful). The compounds showed large Stokes’ shifts, including 195 nm for 6a,b, 240 nm for 6e, and 325 and 352 nm for 6d and 6c, respectively. The highest photoluminescence quantum yield (PLQY) values were observed for 6a,b, which were 15.1 and 12.2%, respectively. The PLQY values for the SP derivatives 6d,e (those with a julolidinyl moiety) were 0.5 and 0.7%, respectively. Cell staining with compound 6e revealed a strong fluorescent signal localised in the cell cytoplasm, whereas the cell nuclei were not stained. SP compound 6e possessed self-assembling properties and formed liposomes with an average diameter of 118 nm. The obtained novel data on near-infrared fluorescent probes could be useful for the development of biocompatible dyes for biomedical applications. Full article
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15 pages, 1835 KiB  
Article
A Novel Flow Cytometry-Based Assay for the Identification of HCN4 CNBD Ligands
by Magdalena N. Wojciechowski, Sebastian Schreiber and Joachim Jose
Pharmaceuticals 2023, 16(5), 710; https://doi.org/10.3390/ph16050710 - 07 May 2023
Viewed by 1501
Abstract
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are promising therapeutic targets because of their association with the genesis of several diseases. The identification of selective compounds that alter cAMP-induced ion channel modulation by binding to the cyclic nucleotide-binding domain (CNBD) will facilitate HCN channel-specific [...] Read more.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are promising therapeutic targets because of their association with the genesis of several diseases. The identification of selective compounds that alter cAMP-induced ion channel modulation by binding to the cyclic nucleotide-binding domain (CNBD) will facilitate HCN channel-specific drug development. In this study, a fast and protein purification-free ligand-binding approach with a surface-displayed HCN4 C-Linker-CNBD on E. coli is presented. 8-Fluo-cAMP ligand binding was monitored by single-cell analysis via flow cytometry, and a Kd-value of 173 ± 46 nM was determined. The Kd value was confirmed by ligand depletion analysis and equilibrium state measurements. Applying increasing concentrations of cAMP led to a concentration-dependent decrease in fluorescence intensity, indicating a displacement of 8-Fluo-cAMP. A Ki-value of 8.5 ± 2 µM was determined. The linear relationship of IC50 values obtained for cAMP as a function of ligand concentration confirmed the competitive binding mode: IC50: 13 ± 2 µM/16 ± 3 µM/23 ± 1 µM/27 ± 1 µM for 50 nM/150 nM/250 nM/500 nM 8-Fluo-cAMP. A similar competitive mode of binding was confirmed for 7-CH-cAMP, and an IC50 value of 230 ± 41 nM and a Ki of 159 ± 29 nM were determined. Two established drugs were tested in the assay. Ivabradine, an approved HCN channel pore blocker and gabapentin, is known to bind to HCN4 channels in preference to other isoforms with an unknown mode of action. As expected, ivabradine had no impact on ligand binding. In addition, gabapentin had no influence on 8-Fluo-cAMP’s binding to HCN4-CNBD. This is the first indication that gabapentin is not interacting with this part of the HCN4 channel. The ligand-binding assay as described can be used to determine binding constants for ligands such as cAMP and derivatives. It could also be applied for the identification of new ligands binding to the HCN4-CNBD. Full article
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17 pages, 1864 KiB  
Article
Synthesis and Biological Evaluation of 6-O-Sucrose Monoester Glycolipids as Possible New Antifungal Agents
by Michele Verboni, Maurizio Sisti, Raffaella Campana, Serena Benedetti, Francesco Palma, Lucia Potenza, Simone Lucarini and Andrea Duranti
Pharmaceuticals 2023, 16(2), 136; https://doi.org/10.3390/ph16020136 - 17 Jan 2023
Cited by 4 | Viewed by 2181
Abstract
A small library of 6-O-sucrose monoester surfactants has been synthesized and tested against various microorganisms. The synthetic procedure involved a modified Mitsunobu reaction, which showed improved results compared to those present in the literature (higher yields and larger scope). The antifungal [...] Read more.
A small library of 6-O-sucrose monoester surfactants has been synthesized and tested against various microorganisms. The synthetic procedure involved a modified Mitsunobu reaction, which showed improved results compared to those present in the literature (higher yields and larger scope). The antifungal activities of most of these glycolipids were satisfactory. In particular, sucrose palmitoleate (URB1537) showed good activity against Candida albicans ATCC 10231, Fusarium spp., and Aspergillus fumigatus IDRAH01 (MIC value: 16, 32, 64 µg/mL, respectively), and was further characterized through radical scavenging, anti-inflammatory, and biocompatibility tests. URB1537 has been shown to control the inflammatory response and to have a safe profile. Full article
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20 pages, 5031 KiB  
Article
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease
by Ignazio Schino, Mariangela Cantore, Modesto de Candia, Cosimo D. Altomare, Catarina Maria, João Barros, Vasco Cachatra, Patrícia Calado, Karina Shimizu, Adilson A. Freitas, Maria C. Oliveira, Maria J. Ferreira, José N. C. Lopes, Nicola A. Colabufo and Amélia P. Rauter
Pharmaceuticals 2023, 16(1), 54; https://doi.org/10.3390/ph16010054 - 30 Dec 2022
Cited by 1 | Viewed by 2063
Abstract
Alzheimer’s Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the [...] Read more.
Alzheimer’s Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N7/N9 linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N9-linked 6-deoxy-α-d-mannosylpurine structure, while all three tested β-d-derivatives appeared as non-selective inhibitors. The N9-linked l-nucleosides were cholinesterase inhibitors except the one embodying either the acetylated sugar or the N-benzyl-protected nucleobase. These findings highlight that sugar-enriched molecular entities can tune bioactivity and selectivity against cholinesterases. In addition, selective copper chelating properties over zinc, aluminum, and iron were found for the benzyl and acetyl-protected 6-deoxy-α-l-mannosyl N9-linked purine nucleosides. Computational studies highlight molecular conformations and the chelating molecular site. The first dual target compounds were disclosed with the perspective of generating drug candidates by improving water solubility. Full article
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Review

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31 pages, 5627 KiB  
Review
Identification and Development of BRD9 Chemical Probes
by Ester Colarusso, Maria Giovanna Chini, Giuseppe Bifulco, Gianluigi Lauro and Assunta Giordano
Pharmaceuticals 2024, 17(3), 392; https://doi.org/10.3390/ph17030392 - 19 Mar 2024
Viewed by 660
Abstract
The development of BRD9 inhibitors involves the design and synthesis of molecules that can specifically bind the BRD9 protein, interfering with the function of the chromatin-remodeling complex ncBAF, with the main advantage of modulating gene expression and controlling cellular processes. Here, we summarize [...] Read more.
The development of BRD9 inhibitors involves the design and synthesis of molecules that can specifically bind the BRD9 protein, interfering with the function of the chromatin-remodeling complex ncBAF, with the main advantage of modulating gene expression and controlling cellular processes. Here, we summarize the work conducted over the past 10 years to find new BRD9 binders, with an emphasis on their structure–activity relationships, efficacies, and selectivities in preliminary studies. BRD9 is expressed in a variety of cancer forms, hence, its inhibition holds particular significance in cancer research. However, it is crucial to note that the expanding research in the field, particularly in the development of new degraders, may uncover new therapeutic potentials. Full article
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36 pages, 6379 KiB  
Review
Photomodulation Approaches to Overcome Antimicrobial Resistance
by Sofia N. Sarabando, Andreia Palmeira, Maria Emília Sousa, Maria Amparo F. Faustino and Carlos J. P. Monteiro
Pharmaceuticals 2023, 16(5), 682; https://doi.org/10.3390/ph16050682 - 02 May 2023
Cited by 1 | Viewed by 1755
Abstract
Photopharmacology is an approach that aims to be an alternative to classical chemotherapy. Herein, the different classes of photoswitches and photocleavage compounds and their biological applications are described. Proteolysis targeting chimeras (PROTACs) containing azobenzene moieties (PHOTACs) and photocleavable protecting groups (photocaged PROTACs) are [...] Read more.
Photopharmacology is an approach that aims to be an alternative to classical chemotherapy. Herein, the different classes of photoswitches and photocleavage compounds and their biological applications are described. Proteolysis targeting chimeras (PROTACs) containing azobenzene moieties (PHOTACs) and photocleavable protecting groups (photocaged PROTACs) are also mentioned. Furthermore, porphyrins are referenced as successful photoactive compounds in a clinical context, such as in the photodynamic therapy of tumours as well as preventing antimicrobial resistance, namely in bacteria. Porphyrins combining photoswitches and photocleavage systems are highlighted, taking advantage of both photopharmacology and photodynamic action. Finally, porphyrins with antibacterial activity are described, taking advantage of the synergistic effect of photodynamic treatment and antibiotic therapy to overcome bacterial resistance. Full article
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