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

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

Deadline for manuscript submissions: closed (20 May 2024) | Viewed by 19881

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Prof. Dr. Amélia Pilar Rauter

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Departamento de Química e Bioquímica (DQB) e Centro de Química Estrutural (CQE), Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
Interests: neurodegenerative diseases; organic synthesis; natural products; antibiotics; antidiabetics; carbohydrate chemistry
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Prof. Dr. Klaus Kopka

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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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Prof. Dr. Thomas Efferth

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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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Prof. Dr. Joachim Jose

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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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Dr. Maria Emília De Sousa

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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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Prof. Dr. Guangshun Wang

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Department of Pathology & Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
Interests: host defense antimicrobial peptides; structural bioinformatics; biomolecular NMR
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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

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11 pages, 260 KiB

Open AccessArticle

The Impact of Chemotherapy on Arterial Stiffness and Ventricular–Arterial Coupling in Women with Breast Cancer

by Nikolaos P. E. Kadoglou, Alexandriani Dimopoulou, Irene Tsappa, Pampina Pilavaki and Anastasia Constantinidou

Pharmaceuticals 2024, 17(9), 1115; https://doi.org/10.3390/ph17091115 - 23 Aug 2024

Viewed by 424

Abstract

Background: The cardiac toxicity of chemotherapy for breast cancer is not uncommon and has been associated with elevated morbidity and mortality. In the present study, we assessed the impact of chemotherapy on cardiovascular function by assessing the cardio–ankle vascular index (CAVI), global longitudinal strain (GLS) and ventricular–arterial coupling (VAC: CAVI/GLS ratio) in chemotherapy-treated women. Methods: This prospective study enrolled 78 women with breast cancer who were receiving anthracycline-based chemotherapy +/− anti-HER2 therapy (trastuzumab +/− pertuzumab). Forty-one age-matched healthy women served as controls. We comparatively evaluated left ventricular ejection fraction (LVEF), CAVI, GLS and VAC, between the chemotherapy and control groups. We also assessed their changes over time (baseline, 3-month and 6-month time point) and their independent association with the incidence of cancer therapy-related cardiovascular dysfunction (CTRCD) in the chemotherapy group. Results: In comparison to healthy controls, women receiving chemotherapy presented with significantly higher GLS (from −21.02 ± 2.09% to −19.01 ± 2.81%, p < 0.001) and VAC (−0.36 ± 0.06 to −0.41 ± 0.11, p < 0.001). The presence of CTRCD was associated with a further increase in GLS and CAVI and a significant decline in LVEF and VAC compared to CTRCD-free women (p < 0.001). Baseline, CAVI, GLS and VAC were independently associated with CTRCD development during follow-up. Conclusion: Women with breast cancer undergoing chemotherapy displayed abnormal levels of CAVI, VAC and GLS, compared to healthy individuals. Those effects on VAC and CAVI were more exaggerated among women with CTRCD, implicating their potential use to refine screening and therapeutic strategies for this specific population. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

25 pages, 5651 KiB

Open AccessArticle

Characterization of Liquid Dosage Forms of Atenolol and Enalapril Maleate for Oral and Enteral Feeding Administration

by Sandra Mota, Ana Torres, Clara Quintas, António M. Peres, Nuno Ferreiro, Rebeca Cruz, Helena Ferreira, Isabel F. Almeida and Susana Casal

Pharmaceuticals 2024, 17(8), 1052; https://doi.org/10.3390/ph17081052 - 9 Aug 2024

Viewed by 645

Abstract

The limited availability of pharmaceutical formulations tailored for cardiovascular diseases in both pediatric and geriatric populations generates the need for compounded dosage forms to guarantee precise dosing and medication adherence. This study aimed to analyze the physicochemical properties and stability of formulations of atenolol and enalapril maleate prepared with a proprietary oral vehicle, SuspendIt^®. To this end, palatability, injectability, pH, rheological behavior, and physical, microbiological, and chemical stability over a 180-day storage period at 25 °C and 5 °C were evaluated. Injectability tests confirmed the suitable use of both formulations for administration through enteral feeding tubes. By using a potentiometric electronic tongue, it was confirmed that the SuspendIt^® vehicle effectively served as a bitter-blocking strategy for atenolol and enalapril maleate. Adequate stability throughout the storage period was confirmed in terms of the mechanical properties, pH, and effectiveness of the preservative system. The atenolol concentration remained above 90% of the initial amount, while the concentration of enalapril maleate decreased to 88% after 90 days of storage at 25 °C. In summary, the atenolol formulation maintained suitable chemical, physical, and microbiological stability after 180 days at both storage temperatures, while the enalapril maleate formulation remained stable up to 60 days at 25 °C and for 180 days at 5 °C. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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67 pages, 15389 KiB

Open AccessArticle

Synthesis and Biochemical Evaluation of Ethanoanthracenes and Related Compounds: Antiproliferative and Pro-Apoptotic Effects in Chronic Lymphocytic Leukemia (CLL)

by James P. McKeown, Andrew J. Byrne, Sandra A. Bright, Clara E. Charleton, Shubhangi Kandwal, Ivan Čmelo, Brendan Twamley, Anthony M. McElligott, Darren Fayne, Niamh M. O’Boyle, D. Clive Williams and Mary J. Meegan

Pharmaceuticals 2024, 17(8), 1034; https://doi.org/10.3390/ph17081034 - 5 Aug 2024

Viewed by 892

Abstract

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells, and it is the most frequent form of leukemia diagnosed in Western countries. It is characterized by the proliferation and accumulation of neoplastic B lymphocytes in the blood, lymph nodes, bone marrow and spleen. We report the synthesis and antiproliferative effects of a series of novel ethanoanthracene compounds in CLL cell lines. Structural modifications were achieved via the Diels–Alder reaction of 9-(2-nitrovinyl)anthracene and 3-(anthracen-9-yl)-1-arylprop-2-en-1-ones (anthracene chalcones) with dienophiles, including maleic anhydride and N-substituted maleimides, to afford a series of 9-(E)-(2-nitrovinyl)-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones, 9-(E)-3-oxo-3-phenylprop-1-en-1-yl)-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones and related compounds. Single-crystal X-ray analysis confirmed the structures of the novel ethanoanthracenes 23f, 23h, 24a, 24g, 25f and 27. The products were evaluated in HG-3 and PGA-1 CLL cell lines (representative of poor and good patient prognosis, respectively). The most potent compounds were identified as 20a, 20f, 23a and 25n with IC₅₀ values in the ranges of 0.17–2.69 µM (HG-3) and 0.35–1.97 µM (PGA-1). The pro-apoptotic effects of the potent compounds 20a, 20f, 23a and 25n were demonstrated in CLL cell lines HG-3 (82–95%) and PGA-1 (87–97%) at 10 µM, with low toxicity (12–16%) observed in healthy-donor peripheral blood mononuclear cells (PBMCs) at concentrations representative of the compounds IC₅₀ values for both the HG-3 and PGA-1 CLL cell lines. The antiproliferative effect of the selected compounds, 20a, 20f, 23a and 25n, was mediated through ROS flux with a marked increase in cell viability upon pretreatment with the antioxidant NAC. 25n also demonstrated sub-micromolar activity in the NCI 60 cancer cell line panel, with a mean GI₅₀ value of 0.245 µM. This ethanoanthracene series of compounds offers potential for the further development of lead structures as novel chemotherapeutics to target CLL. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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13 pages, 2624 KiB

Open AccessArticle

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

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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 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

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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17 pages, 5445 KiB

Open AccessArticle

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 - 6 Jan 2024

Cited by 1 | Viewed by 1802

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 (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

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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26 pages, 10761 KiB

Open AccessArticle

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 - 4 Sep 2023

Viewed by 1280

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 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

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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15 pages, 1835 KiB

Open AccessArticle

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 - 7 May 2023

Viewed by 1922

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 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 K_d-value of 173 ± 46 nM was determined. The K_d 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 K_i-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 K_i 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

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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17 pages, 1864 KiB

Open AccessArticle

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 2591

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 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

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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20 pages, 5031 KiB

Open AccessArticle

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 2373

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 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 N^9-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

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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48 pages, 5287 KiB

Open AccessReview

Future Treatment Strategies for Cancer Patients Combining Targeted Alpha Therapy with Pillars of Cancer Treatment: External Beam Radiation Therapy, Checkpoint Inhibition Immunotherapy, Cytostatic Chemotherapy, and Brachytherapy

by Ruth Christine Winter, Mariam Amghar, Anja S. Wacker, Gábor Bakos, Harun Taş, Mareike Roscher, James M. Kelly and Martina Benešová-Schäfer

Pharmaceuticals 2024, 17(8), 1031; https://doi.org/10.3390/ph17081031 - 5 Aug 2024

Viewed by 771

Abstract

Cancer is one of the most complex and challenging human diseases, with rising incidences and cancer-related deaths despite improved diagnosis and personalized treatment options. Targeted alpha therapy (TαT) offers an exciting strategy emerging for cancer treatment which has proven effective even in patients with advanced metastatic disease that has become resistant to other treatments. Yet, in many cases, more sophisticated strategies are needed to stall disease progression and overcome resistance to TαT. The combination of two or more therapies which have historically been used as stand-alone treatments is an approach that has been pursued in recent years. This review aims to provide an overview on TαT and the four main pillars of therapeutic strategies in cancer management, namely external beam radiation therapy (EBRT), immunotherapy with checkpoint inhibitors (ICI), cytostatic chemotherapy (CCT), and brachytherapy (BT), and to discuss their potential use in combination with TαT. A brief description of each therapy is followed by a review of known biological aspects and state-of-the-art treatment practices. The emphasis, however, is given to the motivation for combination with TαT as well as the pre-clinical and clinical studies conducted to date. Full article

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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31 pages, 5627 KiB

Open AccessReview

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

Cited by 2 | Viewed by 1431

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 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

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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36 pages, 6379 KiB

Open AccessReview

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 - 2 May 2023

Cited by 1 | Viewed by 2349

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 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

(This article belongs to the Special Issue Advances in Pharmaceutical Sciences: In Honor of Dr. Jean Jacques Vanden Eynde (JJ))

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