Publications

What is a Publication?
738 Publications visible to you, out of a total of 738
The Drug Design & Development Seminar 2026: joining forces with the European Cost Action ‘OneHealthDrugs’

Abstract

Not specified

Authors: Simone Haeberlein, Christoph G. Grevelding, Franco H. Falcone, Paul M. Selzer

Date Published: 1st Jul 2026

Publication Type: Journal Article

Synthesis and Evaluation of Nitroheterocyclic Aromatic Adamantanohydrazones with Trypanocidal Activity. Part III

Abstract

Not specified

Authors: Angeliki-Sofia Foscolos, Konstantina Stavropoulou, Nuno Santarém, Anabela Cordeiro da Silva, Martin C. Taylor, Theodora Calogeropoulou, Andrew Tsotinis, Ioannis P. Papanastasiou, John M. Kelly, Susan Wyllie

Date Published: 17th Jun 2026

Publication Type: Journal Article

Synthesis of Methoxylated Benzoxanthones as Drug Metabolites of Antischistosomal Schistodiones—A Limited Environmental Risk

Abstract (Expand)

In the search for new antischistosomal 3-benzylmenadiones (benzylMDs), the screening of a library developed in our laboratory led to the identification of two regioisomeric analogues, the 2′,5′- and … 3′,5′-dimethoxy-benzylMD—designated schistodiones A2′,5′ and A3′,5′—which were investigated for their activity against the platyhelminth Schistosoma mansoni and various protozoan parasites, bacteria, and fungi. Reported work has shown that benzylMDs act as prodrugs: their bioactivation undergoes a cascade of redox reactions within the parasite, generating multiple drug metabolites, e.g., the main benzoylmenadione (benzoylMD) intermediates, and reactive oxygen species that interfere with key metabolic pathways. Among the secondary metabolites, benzoxanthones have been identified as potential products generated along this oxidative pathway. The aim of the study was to synthetize methoxylated benzoxanthones, as putative metabolites generated from these antischistosomal benzylMDs. During the synthetic work, several difficulties arose, including the absence of starting reagents, the incompatibility of certain reactions with methoxy groups, the possible formation of several isomers, and the easy re-oxidation of sensitive intermediates. To overcome these obstacles, we developed a new retrosynthetic strategy using modified precursors: replacing methoxy groups with O-methylenemethoxy (OMOM) groups that are more stable in basic media, using aldehydes or aromatic esters as precursors, and replacing certain substituents with groups that are easier and less costly to introduce (chlorine or nitro). Selected metabolites (benzoylMDs, benzoxanthones) were then tested in parasite and cellular assays. Furthermore, benzoylMDs were tested as subversive substrates of S. mansoni thioredoxin-glutathione reductase (SmTGR) and selected drug metabolites were investigated in SmTGR modeling experiments. From a One Health perspective, these benzylMD derivatives pose limited environmental risk because their metabolites lack toxicity when encountered externally, as toxicity requires intracellular metabolic activation and localized formation of reactive intermediates in close proximity to their cellular targets inside parasites.

Authors: Elena Cesar-Rodo, Jeremy Boilevin, Jimmy Richard, Peter D. Ziniel, Didier Belorgey, Louis Maes, Francesco Angelucci, David Lee Williams, Elisabeth Davioud-Charvet, Don Antoine Lanfranchi

Date Published: 27th May 2026

Publication Type: Journal Article

Environmentally Safe and Just Pharmacy: A Framework and Action Plan for Operating within the Earth System Boundary for Novel Entities

Abstract

Not specified

Authors: Alistair B. A. Boxall, Priyanie Amerasinghe, Sally Beckenham, Michael G. Bertram, Sally Gaw, Austin D. Gray, Karen A. Kidd, Laura M. Langan, Kenneth M. Y. Leung, Jack L. Manera, Karina S. B. Miglioranza, Rik Oldenkamp, Bryan W. Brooks

Date Published: 7th May 2026

Publication Type: Journal Article

A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 3: from lead towards a drug development candidate

Abstract (Expand)

Abstract Neglected tropical diseases such as leishmaniasis, Chagas disease, sleeping sickness and animal trypanosomiasis remain a significant global health challenge. This part of the roadmap outlines …e roadmap outlines a streamlined path for progressing from lead identification to a drug development candidate, tailored to the specific needs of kinetoplastid infections. Besides the medicinal upscaling of synthesis, this review highlights key experiments in pharmacology in non-rodent species, toxicology, pharmacokinetics and pharmaceutics. These include but are not limited to early evaluation of safety using refined in vitro and in vivo methods to enhance predictive value, bioavailability and distribution to target tissues, and formulation strategies leveraging various delivery systems to optimize efficacy and safety. Environmental toxicity is also addressed proactively, for which in silico tools are presented. Collectively, this roadmap provides a practical, scalable approach to deliver high-quality drug candidates capable of addressing the urgent needs for kinetoplastid diseases (Figure 1).

Authors: Sarah Hendrickx, Kayhan Ilbeigi, Eli S J Thoré, Michael G Bertram, Estefanía Calvo-Alvarez, Sener Cintesun, Ana Isabel Olías-Molero, María Jesús Corral, Marta Mateo-Barrientos, Jérôme Estaquier, Sébastien Pomel, José María Alunda, Sheraz Gul, Katrien Van Bocxlaer, Frédéric Frézard, Joana Tavares, Anabela Cordeiro Da Silva, Maria Paola Costi, Louis Maes, Guy Caljon

Date Published: 5th May 2026

Publication Type: Journal Article

The EamA metabolite transporter does not affect antileishmanial drug susceptibility.

Abstract (Expand)

Leishmaniasis is a major neglected tropical disease, exists in 98 countries and constitutes a global public health threat. As chemotherapy is confronted with drug resistance and treatment failure, … understanding the underlying mechanisms and continued drug discovery efforts are needed in the fight against leishmaniasis. A previous cosmid-based overexpression study suggested a role for EamA (LINF_020008400), annotated as a putative drug-metabolite transporter, in resistance to novel antileishmanial oxaboroles. To assess fitness cost and drug susceptibility, gene deficient Leishmania infantum lines were generated using CRISPR-Cas9 gene editing and overexpression from the ssu locus was achieved using the pLEXSY system. While in vitro parasite growth and survival were unchanged compared to control lines, the intracellular burden of the null mutant was lower. In vitro exposure to current antileishmanial drugs and several novel leads revealed an unchanged drug sensitivity profile in extracellular and intramacrophage assays. Similarly, the overexpression lines showed a significantly lower infection rate, but their drug susceptibility profiles showed no significant differences from the control. Collectively, these data suggest that -under the tested conditions- LINF_020008400 is not essential for parasite fitness, host cell infectivity and survival following exposure to antiparasitic drugs.

Authors: R. Ahmad, G. Gastoldi, S. T. Wong, A. Baeza Garcia, G. Caljon

Date Published: 19th Apr 2026

Publication Type: Journal Article

A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 1: setting the stage

Abstract (Expand)

Abstract Given the impact of kinetoplastid diseases, the limited therapeutic options and risk of treatment failure, continued research efforts to discover novel drug entities are required. The ambition …ired. The ambition to deliver drug development candidates has mainly been taken on board by academia and public private partnerships, but remains highly challenging because of the lack of adequate funding and standardized laboratory procedures. Establishing a systematic roadmap of experiments and decision criteria to attain high-quality leads and drug candidates with lower risk profiles remains the logical path to deliver more compelling proof-of-concepts for impactful diseases, such as African trypanosomiasis, Chagas disease and visceral and cutaneous leishmaniasis. In a three-part series, a structured roadmap from ‘hit finding’ to ‘drug development candidate’ is presented with a focus on the minimal essential data package, laboratory experimental models and endpoints. Part 1 introduces the concept of a pragmatic framework with reference to specific preclinical R&D stages: (i) hit finding, (ii) hit profiling, (iii) lead definition and (iv) drug development candidate to support a more focused early development path that remains accessible to engaged stakeholders. The experiment-oriented roadmap is presented in the next parts addressing the discovery and characterization of confirmed hits (Part 2) and the lead discovery phase towards identification of a drug development candidate (Part 3). Although specifically focusing on kinetoplastid diseases, the principles also apply to small-molecule preclinical R&D against other microbial diseases, evidently with specific adaptation of the primary pharmacology models.

Authors: Sarah Hendrickx, Kayhan Ilbeigi, Eli S J Thoré, Michael G Bertram, Estefanía Calvo-Alvarez, Sener Cintesun, Ana Isabel Olías-Molero, María Jesús Corral, Marta Mateo-Barrientos, Jérôme Estaquier, Sébastien Pomel, José María Alunda, Sheraz Gul, Katrien Van Bocxlaer, Frédéric Frézard, Joana Tavares, Anabela Cordeiro Da Silva, Maria Paola Costi, Louis Maes, Guy Caljon

Date Published: 3rd Apr 2026

Publication Type: Journal Article

The application of ultrastructure expansion microscopy reveals the apical microtubule architecture of Babesia

Abstract

Not specified

Authors: Viktoriya Levytska, Alexey Bondar, Ana Maria Filipe, Jana Kopecka, Daniel Sojka, Marie Jalovecka

Date Published: 1st Apr 2026

Publication Type: Journal Article

Multifaceted biological and computational assessment of aromatic and N-heteroaromatic non-substituted thiosemicarbazones.

Abstract (Expand)

Thiosemicarbazones (TSCs) constitute a pharmacologically versatile class of compounds with documented antimicrobial, antiviral, and anticancer properties. Despite their therapeutic potential, their … biological mechanisms and pharmacokinetic behaviour remain insufficiently characterized. In this study, we investigated the biological activity of the library consisting of 28 aromatic and heteroaromatic compounds against twelve cancer cell and two normal cell lines, and four parasites. Six N-heteroaromatic thiosemicarbazones based on pyridine (13, 14, and 18), quinoline (24 and 26), and indole (27) moieties show promising anticancer and/or antiparasitic activity. Density functional theory (DFT) calculations indicated that the biological activity of 13, 14, 18, 24, and 26 arises from their ability to chelate d-metals, whereas 27 operates via a distinct mechanism. The passive gastrointestinal absorption and Human serum albumin (HSA) binding ability of these six compounds were evaluated by the Parallel artificial membrane permeability (PAMPA) technique and high-performance affinity chromatography, respectively. Compound 26 emerged as the most potent and selective anticancer agent and was further examined through cell cycle profiling, caspase-3/7 activation, DNA double-strand break quantification, 3D spheroid assays, and an in ovo chorioallantoic membrane (CAM) model, supported by HSA docking and molecular dynamics simulations. Collectively, our results indicate that 26 is a selective anticancer agent that exerts cytotoxic effects preferentially in cancer cells, by inducing apoptosis and DNA double-strand breaks.

Authors: N. Macijewska, P. Ristic, A. Kallingal, M. Gulea, M. Donnard, N. Girard, A. Matheeussen, N. Van Pelt, G. Caljon, V. Dobricic, J. Boskovic, M. Popovic-Nikolic, K. Nikolic, M. Zloh, V. Blagojevic, T. Todorovic, N. Filipovic

Date Published: 25th Mar 2026

Publication Type: Journal Article

Metabolic thermodynamics: pertinent reference state and energy potentials

Abstract (Expand)

Chemical potentials (molar Gibbs energies) are usually extrapolated to the remote physical–chemical reference state and then stored. Subsequent use under in vivo conditions requires a similarly … conditions requires a similarly substantial, reverse extrapolation, again with significant potential errors. In order to shrink both extrapolations drastically and thereby enhance both biological meaning and accuracy, we propose a transformation to a more biological reference state: pH = 7, pMg = 3, 99.5% water, with 1 m m each of the additional ‘precursors’ inorganic phosphate, sulfate, ammonium, and bicarbonate, and with twin temperatures 37 and 25 °C, ionic strength 0.15  m and m m as concentration unit. These precursors substitute for reference compounds alien to biology such as H 2 at 1 bar, and solid graphite, sulfur, and phosphorus. The standard chemical potentials are herewith increased by the magnitudes of the chemical potentials of protons, Mg 2+ , water, and the four precursors, each multiplied by the number of corresponding atoms in the molecule. This defines standard ‘metabolic potentials’. We make these potentials findable and accessible as 1360 collated standard chemical potentials for 320 compounds of biochemical interest at the twin metabolic reference states. We do this for 3 reference pH's: We present the metabolic reference state as a convenient anchor , not a universal intracellular milieu. All datasets must continue to report the actual experimental state ( T , pH, pMg, I , osmolarity, concentrations), yet aim at (also) reporting parameter values for this anchor state; we supply algorithms to transform between states. This preserves interoperability across diverse organelles, media and between enzymology and chemical engineering, while facilitating reuse.

Authors: Hans V. Westerhoff, Barbara M. Bakker, Andreas S. Bommarius, Maria Luz Cárdenas, Athel Cornish‐Bowden, Paul Fitzpatrick, Peter J. Halling, Vassily Hatzimanikatis, Carsten Kettner, Yanhua Liu, Andrew G. McDonald, Elad Noor, Jürgen Pleiss, Frank M. Raushel, Johann M. Rohwer, Santiago Schnell, Keith F. Tipton, Ming‐Daw Tsai, Urs von Stockar, Ulrike Wittig, Roland Wohlgemuth, John M. Woodley

Date Published: 5th Mar 2026

Publication Type: Journal Article

A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 2: from molecule to confirmed hit

Abstract (Expand)

Abstract Given the medical importance and challenges related to kinetoplastid diseases, a strategic roadmap is needed for the identification of high-quality leads and drug development candidates. Within …candidates. Within the aim to deliver more compelling proof-of-concept read-outs, this part proposes a systematic flow-chart of laboratory experiments and decision criteria, focusing on African trypanosomiasis, Chagas disease and visceral and cutaneous leishmaniasis. Next to precision experimental design and reporting, an overview is provided of various complementary laboratory models reproducing kinetoplastid infection and disease. Technical aspects of conventional in vitro and in vivo approaches and, more recently, in silico methods are presented with reference to specific preclinical R&D stages from ‘hit finding’ to ‘profiling of a confirmed hit’, covering the expertise areas of medicinal chemistry, primary pharmacology, (eco)toxicology, pharmacokinetics and pharmaceutics (Figure 1).

Authors: Sarah Hendrickx, Kayhan Ilbeigi, Eli S J Thoré, Michael G Bertram, Estefanía Calvo-Alvarez, Sener Cintesun, Ana Isabel Olías-Molero, María Jesús Corral, Marta Mateo-Barrientos, Jérôme Estaquier, Sébastien Pomel, José María Alunda, Sheraz Gul, Katrien Van Bocxlaer, Frédéric Frézard, Joana Tavares, Anabela Cordeiro Da Silva, Maria Paola Costi, Louis Maes, Guy Caljon

Date Published: 4th Mar 2026

Publication Type: Journal Article

Cytotoxicity and Antimicrobial Activity of GaMF1 Analogs.

Abstract (Expand)

Recent studies have identified the mycobacterial adenosine triphosphate synthase inhibitor GaMF1 and its structural analogs as compounds with noteworthy antituberculosis activity. Despite these promising … results, a significant limitation remains their cytotoxicity against human cells, which, in its current state, overshadows the therapeutic potential. Therefore, addressing this off-target toxicity is essential for the further development of these compounds as viable drug candidates. In this study, we systematically explored structural modifications of the original GaMF1 scaffold with the primary aim of reducing its inherent cytotoxicity. Individual regions of the parent structure were progressively replaced, enabling the identification of substituents that effectively attenuate cytotoxic effects. Importantly, these structural refinements also led to the emergence of pronounced antiparasitic activity, particularly against trypanosomal species such as Trypanosoma cruzi, Trypanosoma brucei brucei, and Trypanosoma brucei rhodesiense. These findings suggest that the biological potential of this compound class extends beyond what has previously been described. Furthermore, we evaluated the cytotoxicity of selected derivatives against a panel of tumor cell lines, where some compounds showed encouraging antiproliferative effects.

Authors: J. Chasak, P. Vyvlecka, I. Nemec, A. Matheeussen, N. Van Pelt, P. Cos, G. Caljon, V. Krystof, L. Brulikova

Date Published: 25th Feb 2026

Publication Type: Journal Article

Energetic stress in combination with impaired fatty acid oxidation induces sequestration of <scp>CoA</scp> and adaptation of <scp>CoA</scp> metabolism

Abstract (Expand)

Coenzyme A (CoA) is a vital cofactor involved in 8–10% of all metabolic reactions in human cells. Different inherited enzyme deficiencies in which the oxidation of acyl‐CoAs is hampered have been … hypothesised to share a phenotype characterised by toxic accumulation of acyl‐CoA and a concomitant decline in free CoA (CoASH) levels, whereby CoASH becomes limiting for other metabolic reactions. This is referred to as CoASH sequestration. There is, however, limited experimental evidence for this hypothesis. Using a combination of approaches, we test this hypothesis in medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD), the most common deficiency of mitochondrial fatty acid oxidation (mFAO), under energetic stress. Both in vitro MCAD‐knockout (KO) HepG2 cells and a kinetic model of mFAO showed decreased CoASH, elevated medium‐chain acyl‐CoA, and decreased long‐chain acyl‐CoA levels. MCAD‐KO mice exposed to fasting and cold as energetic stressors had a significantly increased total CoA pool and increased expression of CoA biosynthetic enzymes in the liver, indicative of an upregulated CoA biosynthesis. Expression of carnitine acyltransferases and acyl‐CoA thioesterases, enzymes that liberate CoASH from acyl‐CoAs, was also upregulated, suggesting an adaptive response of CoA metabolism to decreased CoASH. Finally, computational model simulations showed that a combination of elevated total CoA and thioesterase activity led to normalisation of both CoASH and medium‐chain acyl‐CoA levels. Together, the results provide the first evidence for the CoA sequestration hypothesis in MCADD. The observed adaptation of CoA metabolism under energetic stress may act as a compensatory response that counteracts CoASH depletion and accumulation of toxic medium‐chain acyl‐CoAs.

Authors: Ligia Akemi Kiyuna, Christoff Odendaal, Madhulika Singh, Albert Gerding, Miriam Langelaar‐Makkinje, Marianne van der Zwaag, Asmara Drachman, Vladimíra Cetkovská, Gaby Liem Foeng Kioen, Anne‐Claire M. F. Martines, Nicolette C. A. Huijkman, Hein Schepers, Bart van de Sluis, Dirk‐Jan Reijngoud, Ody C. M. Sibon, Amy C. Harms, Thomas Hankemeier, Barbara M. Bakker

Date Published: 7th Feb 2026

Publication Type: Journal Article

The heme A synthase Cox15, as a target of redox-active 3-benzylmenadiones with antiparasitic activity

Abstract (Expand)

ABSTRACT Chagas disease, caused by Trypanosoma cruzi , is a neglected parasitic infection. The very limited arsenal of anti- T . cruzi treatments calls for the development of new drugs. Recently, a …sitic infection. The very limited arsenal of anti- T . cruzi treatments calls for the development of new drugs. Recently, a library of 3-benzylmenadione derivatives was synthesized, with cruzidione being the most efficient and specific compound against the parasite. To decipher its mode of action, we used the yeast Saccharomyces cerevisiae as a model. Evidence pinpointed at the heme A synthase Cox15 as a primary target of cruzidione: (i) a mutation in Cox15 (i.e., S429F) renders the yeast cells highly sensitive to the drug, (ii) treatment with cruzidione led to the loss of cytochrome c oxidase, an enzyme that relies on heme A as an essential cofactor, and (iii) replacement of the yeast Cox15 by T. cruzi enzyme resulted in a high sensitivity to cruzidione. We then investigated the effect of cruzidione in T. cruzi and observed a significant reduction in the heme contents, most likely involving the inhibition of the heme A synthase. This, in turn, led to a decrease in O 2 consumption by the parasite. Finally, using the yeast model, we showed that, similar to what we previously found for the antimalarial benzylmenadione plasmodione, NADH-dehydrogenase plays a key role in cruzidione bioactivation. We proposed that the reduced benzoylmenadione metabolites, produced by the reaction with NADH-dehydrogenase, act as Cox15 inhibitors. This study, through the identification of the mode of action of cruzidione, highlighted Cox15 as a novel target for antiparasitic drugs.

Authors: Marcelo L. Merli, Claudia Serot, Cindy Vallières, Julia A. Cricco, Bogdan I. Iorga, Elisabeth Davioud-Charvet, Brigitte Meunier

Date Published: 7th Jan 2026

Publication Type: Journal Article

Oxyprenyl–chalcones as antibacterial hits: design of experiments-optimized synthesis, antibacterial evaluation, early drug-like profiling and biodegradability prediction

Abstract

The escalating threat of antimicrobial resistance (AMR) compels the development of novel antibiotics with broad spectrum activity and environmentally responsible degradation profiles.

Authors: Ludovica Marotta, Francesca Maria Pia Rita Giammarino, Brondon Brandly Senenou Tambou, Valeria Tudino, Stefania Butini, Lorenza Broccardo, Sacha Michèle Idriss Cancade, Jean-Denis Docquier, Federica Perego, Nicoletta Basilico, Lorenzo Raffellini, Sheraz Gul, Gabriele Carullo, Sandra Gemma, Giuseppe Campiani

Date Published: 2026

Publication Type: Journal Article

Syntheses and computational analyses of selected macrolide derivatives derived from clarithromycin A

Abstract (Expand)

This study presents the synthesis and experimental and computational analysis of novel macrolide derivatives obtained from clarithromycin A, with the aim of exploring their potential to address the … growing problem of antimicrobial resistance. The compounds synthesized include 2?-O-acetyl-clarithromycin A, its phosphoramidite derivative, and the corresponding phosphonyl derivative. Special attention was paid to the optimization of phosphitylation conditions due to the inherent instability of phosphoramidite compounds. The purity of the phosphoramidite derivative was successfully confirmed using diffusion-ordered NMR spectroscopy (DOSY). Comprehensive conformational analyses were carried out using molecular modeling techniques, followed by molecular docking and MM-GBSA calculations with a target protein from Escherichia coli to evaluate the relative binding affinities of clarithromycin A and its derivatives. The results indicate that the phosphoramidite and phosphonyl derivatives exhibit comparable binding affinities relative to the parent antibiotic. In addition, complex mass spectrometric fragmentation patterns of the phosphorus-containing derivatives were analyzed and rationalized using the MS Fragmenter computational tool.

Authors: Biljana Arsic, Gareth Morris, Abdolreza Hassanzadeh, Olga Jovanovic, Jill Barber, Djordje Glisin

Date Published: 2026

Publication Type: Journal Article

Synthesis and evaluation of nitroheterocyclic aromatic adamantane amides with trypanocidal activity. Part II

Abstract

New nitroheterocyclic adamantane amides display promising trypanocidal activity. The spacer length between the adamantylphenyl backbone and the nitroheterocyclic ring plays a crucial role in potency.

Authors: Angeliki-Sofia Foscolos, Richard L. Atherton, Maria Billia, Markos-Orestis Georgiadis, Nuno Santarém, Anabela Cordeiro da Silva, Martin C. Taylor, John M. Kelly, Theodora Calogeropoulou, Andrew Tsotinis, Thomas Mavromoustakos, Ioannis P. Papanastasiou

Date Published: 2026

Publication Type: Journal Article

Are Behavioral Ecotoxicity Endpoints Relevant at the Population Level? Evidence-Based Insights for Environmental Protection

Abstract

Not specified

Authors: Michael G. Bertram, Marlene Ågerstrand, Sigal Balshine, Jack A. Brand, Bryan W. Brooks, ZhiChao Dang, Alex T. Ford, Henner Hollert, Matthew K. LeFauve, Jack L. Manera, Jake M. Martin, Marcus Michelangeli, Maria Moiron, Eleanor R. Moore, Holly J. Puglis, Andrew Sih, Jeffery A. Steevens, Eli S. J. Thoré, Bob B. M. Wong, Lauren Zink, Tomas Brodin

Date Published: 24th Dec 2025

Publication Type: Journal Article

BioHackEU25 report: Towards a Robust Validation Service for Data and Metadata in ARC RO-Crates

Abstract (Expand)

<p>Robust validation of both research data and its accompanying metadata is essential for ensuring adherence to FAIR principles. Current approaches often handle these aspects separately, hindering … a holistic quality assessment. Building upon previous BioHackathon work establishing ARCs (Annotated Research Context) as RO-Crates (ARC RO-Crate), we aim to develop and demonstrate an integrated validation strategy for FAIR digital objects. It distinguishes between validating the metadata descriptor and the payload data files.For the metadata descriptor, validation will ensure structural and semantic compliance to the base RO-Crate specification and the ARC-ISA family of RO-Crate profiles, using and extending the RO-Crate validator tool.For the payload data files, validation targets the actual content, since data files often require domain-specific structural and value constraints, which requires explicit schema definitions. For this, we will integrate Frictionless for checking data content against community standards (e.g. MIAPPE, as demonstrated in the HORIZON project AGENT). Crucially, this project will also explore mechanisms for specifying expected data structures’ requirements within the ARC RO-Crate itself. This aims to provide a more self-contained description of data, investigating how such internal requirements can be linked to data validation frameworks, complementing the crate’s metadata validation.The overall goal is to provide a powerful, holistic validation mechanism for ARC RO-Crates, enhancing their reliability, trustworthiness, and FAIRness. A MIAPPE-compliant plant phenomics dataset will serve as a use case. This integrated validation approach aims to streamline quality control for researchers and will be packaged as a deployable microservice, offering broad applicability across diverse research workflows.</p>

Authors: Eli Chadwick, Matthijs Brouwer, Kevin Schneider, Daniel Arend, Finn Bacall, Etienne Bardet, Sebastian Beier, Dominik Brilhaus, Xiaoming Hu, Emma Le Roy Pardonche, Timo Mühlhaus, Stuart Owen, Cyril Pommier, Heinrich Lukas Weil

Date Published: 16th Dec 2025

Publication Type: Report

From pan-active to parasite-selective antiparasitic agents: A scaffold hopping approach

Abstract

Not specified

Authors: Chiara Borsari, Nuno Santarem, Dina Coertzen, Asia Mazzolari, Alexandra Ioana Corfu, Catarina Coelho, Francisca Barbosa, Lucia Tamborini, Lyn-Marié Birkholtz, Lorenzo Raffellini, Oliver Keminer, Nicoletta Basilico, Silvia Parapini, Sheraz Gul, Anabela Cordeiro-da-Silva, Paola Conti

Date Published: 1st Dec 2025

Publication Type: Journal Article

Thiazolidinones and related analogues as efficient antitrypanosomal agents.

Abstract (Expand)

We designed and synthesised a series of thiazolidinediones and related analogues and evaluated their antiparasitic activity. A structure-activity relationship (SAR) study focused on modifications of … specific parts of the molecule revealed derivatives that displayed significant activity against Trypanosoma brucei species. Notably, the analogue 6i exhibited exceptional activity, with an EC(50) value of 30 nM and a selectivity index of >2000, against the protozoan Trypanosoma brucei rhodesiense, which causes human African trypanosomiasis. Additionally, compounds 6a, 6k, 7e, and 18 demonstrated antitrypanosomal activities in the less than 5 muM range. Our most active analogue 6i represents a promising candidate for further preclinical development.

Authors: M. Kolarik, K. Ilbeigi, G. Caljon, L. Brulikova

Date Published: 1st Dec 2025

Publication Type: Journal Article

Persistent myeloid cell reprogramming despite miltefosine treatment in leishmania-infected macaques

Abstract

Not specified

Authors: Morgane Picard, Steven Boutrais, Vasco Rodrigues, Yasmina Fortier, Chloé Borde, Calaiselvy Soundaramourty, Julien Clain, Charles Joly-Beauparlant, Gina Racine, Ouafa Zghidi-Abouzid, Arnaud Droit, Alain Pruvost, Maria Paola Costi, Ricardo Silvestre, Anabela Cordeiro da Silva, Jane MacDougall, Sónia André, Jérôme Estaquier

Date Published: 1st Dec 2025

Publication Type: Journal Article

Π-Π stacking stabilized polymeric micelles for hydrophobic drug delivery in the treatment of leishmaniasis

Abstract

Not specified

Authors: Ana G. Gomes-Alves, Aida Varela-Moreira, Tânia Cruz, Margarida Duarte, Helena Castro, Rui Moreira, Ana S. Ressurreição, Gert Storm, Wim E. Hennink, Ana M. Tomás

Date Published: 1st Dec 2025

Publication Type: Journal Article

Design of 2-Aminobenzothiazole Derivatives Targeting Trypanosomatid PTR1 by a Multidisciplinary Fragment Hybridization Approach.

Abstract (Expand)

Pteridine reductase 1 (PTR1) is a folate pathway enzyme essential for pathogenic trypanosomatids and a promising drug target for diseases such as sleeping sickness and leishmaniasis. Previous studies … have shown that the 2-aminobenzothiazole moiety targets the PTR1 biopterin pocket, while 3,4-dichlorophenyl-containing compounds, such as I bind a different region of the Trypanosoma brucei PTR1 (TbPTR1) pocket. This study combines both moieties via various linkers, creating two compound series screened in silico against TbPTR1 and Leishmania major PTR1 (LmPTR1). In the first series, five compounds were synthesized, and 1a and 1b emerged as potent TbPTR1 inhibitors, with 1b also being active against LmPTR1 and moderately effective against Leishmania infantum. Furthermore, structure-activity relationship analysis, supported by quantum calculations and crystallography, revealed meta-halogenation to be more favorable than para, although single halogenation reduced antiparasite effects. Our fragment hybridization approach led to less toxic, more effective compounds than I.

Authors: J. Panecka-Hofman, P. Linciano, I. Pohner, E. Dyguda-Kazimierowicz, W. Jedwabny, G. Landi, N. Santarem, G. Witt, B. Ellinger, M. Kuzikov, R. Luciani, S. Ferrari, D. Aiello, S. Mangani, C. Pozzi, A. Cordeiro-da-Silva, S. Gul, M. P. Costi, R. C. Wade

Date Published: 9th Oct 2025

Publication Type: Journal Article

Long-Circulating Liposomes Codelivering Amphotericin B and Retinoic Acid for Cutaneous Leishmaniasis Treatment

Abstract

Not specified

Authors: Thais T. Santos, Eduardo B. Lages, Tiago N. Q. Ricotta, Leandro G. de Oliveira, Guilherme S. Ramos, Julie Burlot, Sonia Abreu, Pierre Chaminade, François-Xavier Legrand, Pauline Tran, Claudine Deloménie, Virgínia M. R. Vallejos, Doumet Georges Helou, Raquel M. de Almeida, Celso M. Queiroz-Junior, Gabriel B. M. Teobaldo, Cristiano L. P. de Oliveira, Lucas A. M. Ferreira, Marta M. G. Aguiar, Sébastien Pomel, Frédéric Frézard

Date Published: 7th Oct 2025

Publication Type: Journal Article

AgamOBP1‐Directed Discovery of Repellents to Control the Spread of Mosquito‐Borne Diseases

Abstract (Expand)

Toward the discovery of novel efficient repellents, protein‐directed dynamic combinatorial chemistry (pdDCC) coupled to saturation‐transfer difference (STD) NMR spectroscopy was initially employed to … identify modulators of the malaria vector Anopheles gambiae Odorant Binding Protein 1 (AgamOBP1). A library of potential binders of AgamOBP1 (secondary amines) generated from two amines and seven aldehydes was designed aiming to enable interactions with critical amino acids at the DEET‐site and to bridge the DEET‐ and Icaridin sIC‐binding pockets, both implicated in repellents recognition. Solubility issues hindered the clear identification of binders among the DCL members, except for one sublibrary, leading us to shift our strategy towards the synthesis of the designed amines, followed by direct evaluation of their binding to AgamOBP1 using 1 H STD NMR spectroscopy. The identified binders were further validated in vitro by fluorescence competition assays, and the most potent compounds which also possessed suitable vapor pressure were evaluated as repellents in arm‐in‐cage behavioral assays against Aedes albopictus . Amines 2A , 3A , 4A , and 6A showed significant repellent activity. The most potent was compound 4A (4‐methyl‐ N ‐(pyridin‐4‐ylmethyl)aniline) which acted as a a DEET‐like repellent at 0.4 μL cm − 2 dose. Thus, our strategy showcased a promising scaffold for further optimization toward efficient mosquito repellents.

Authors: Evanthia Chazapi, Eftichia Kritsi, Constantinos Potamitis, Panagiota G. V. Liggri, Katerina E. Tsitsanou, Christina E. Drakou, Antonios Michaelakis, Dimitrios P. Papachristos, Spyros E. Zographos, Maria Zervou, Theodora Calogeropoulou

Date Published: 21st Sep 2025

Publication Type: Journal Article

Sustainable Antiparasitic Agents from an Agro-Industrial Waste: Mitochondria-Targeting Cashew Nutshell Liquid-Derived Phosphonium and Ammonium Salts

Abstract

Not specified

Authors: Bianca Martinengo, Cecilia Baldassarri, Kayhan Ilbeigi, Hamed E. Alkhalaf, Aditya Sarode, Ehab Kotb Elmahallawy, Ba Reum Kwon, Amos Sarpong Agyei, Aigerim Abdimanova, Ludmila Ferreira de Almeida Fiuza, Raquel Azevedo, Ketlym da Conceição, Marcos Meuser Batista, Ellyêssa Nascimento Borges, Kleber Santiago Freitas e Silva, Éder Jéferson Souza Cardoso, Natália Cipriano Monteiro, Lais Flavia Nunes Lemes, Luiz Antonio Soares Romeiro, Antonio Alonso, Maria de Nazaré Correia Soeiro, Guy Caljon, Bryan W. Brooks, Harry P. De Koning, Maria Laura Bolognesi

Date Published: 8th Sep 2025

Publication Type: Journal Article

Drug Repurposing for Kala-Azar

Abstract (Expand)

Objective: Visceral leishmaniasis (VL), a Neglected Tropical Disease caused by Leishmania donovani, remains insufficiently addressed by current therapies due to high toxicity, poor efficacy, and … immunosuppressive complications. This study aimed to identify and characterize repurposed drugs that simultaneously target parasite-encoded and host-associated mechanisms essential for VL pathogenesis. Methods: Two complementary in silico drug repurposing strategies were employed. The first method utilized electron–ion interaction potential (EIIP) screening followed by molecular docking and molecular dynamics (MD) simulations targeting two L. donovani proteins: Rab5a and pteridine reductase 1 (PTR1). The second approach employed network-based drug repurposing using the Drugst.One platform, prioritizing candidates via STAT3-associated gene networks. Predicted drug–target complexes were validated by 100 ns MD simulations, and pharmacokinetic parameters were assessed via ADMET profiling using QikProp v7.0 and SwissADME web server. Results: Entecavir and valganciclovir showed strong binding to Rab5a and PTR1, respectively, with Glide Scores of −9.36 and −9.10 kcal/mol, and corresponding MM-GBSA ΔG_bind values of −14.00 and −13.25 kcal/mol, confirming their stable interactions and repurposing potential. Network-based analysis identified nifuroxazide as the top candidate targeting the host JAK2/TYK2–STAT3 axis, with high stability confirmed in MD simulations. Nifuroxazide also displayed the most favorable ADMET profile, including oral bioavailability, membrane permeability, and absence of PAINS alerts. Conclusions: This study highlights the potential of guanine analogs such as entecavir and valganciclovir, and the nitrofuran derivative nifuroxazide, as promising multi-target drug repurposing candidates for VL. Their mechanisms support a dual strategy targeting both parasite biology and host immunoregulation, warranting further preclinical investigation.

Authors: Biljana Arsić, Budimir S. Ilić, Andreas Maier, Michael Hartung, Jovana Janjić, Jelena Milićević, Jan Baumbach

Date Published: 6th Aug 2025

Publication Type: Journal Article

Human Dialyzable Leukocyte Extract Enhances Albendazole Efficacy and Promotes Th1/Th2-Biased Lymphocyte and Antibody Responses in Peritoneal Cavity of Murine Model of Mesocestoides vogae Infection

Abstract (Expand)

Human leukocyte extract (HLE), a non-immunogenic dialyzable leukocyte preparation (<10 kDa), may serve as a safe adjuvant in immunotherapy. We investigated the effects of albendazole (ABZ), HLE, and … their combination in Mesocestoides vogae infected mice, focusing on lymphoid cells in the peritoneal cavity, the site of larval proliferation and parasite-induced immunosuppression. Peritoneal lymphoid cells were analysed by flow cytometry and qPCR. Cells proliferative responses to ConA, LPS, and parasite excretory/secretory (E/S) antigens, cytokine production (ELISA), IgM and IgG isotypes in exudates and parasite antigen recognition (Western blot) were assessed. Efficacy was measured by larval burden and 14-3-3 gene expression in larvae. HLE combined with ABZ enhanced larval clearance and suppressed 14-3-3 gene expression in larvae. HLE and combination therapy increased CD3+ T cell frequencies, especially CD3+high, reduced regulatory CD3+/IL-10 Tregs and expression of Foxp3+. All treatments diminished CD19+/IL-10+ Bregs, correlating with lower CD9 and Atf3 mRNA levels compared to infected mice. Transcription factors T-bet expression was strongly upregulated, while GATA3 was moderately elevated. IFN-γ production and T/B cell proliferation were restored after HLE and combination therapy, partially, even in the presence of E/S antigens. IgM and total IgG levels against parasite antigens declined, while Th1-associated IgG2a increased in ABZ+HLE and HLE-treated groups. Albendazole failed to reverse the immunosuppressive Treg-type immunity but was more effective in reducing Breg populations and their functions. HLE enhanced ABZ efficacy by restoring Th1 responsiveness, reducing Treg/Breg activity, and modulating antibody profiles. It represents a promising immunomodulatory adjuvant in the treatment of the infections associated with Th2/Treg-driven immunosuppression.

Authors: Gabriela Hrčková, Dagmar Mudroňová, Katarína Reiterová, Serena Cavallero, Ilaria Bellini

Date Published: 21st Jul 2025

Publication Type: Journal Article

Diverse Metabolic Control of Phosphoglucomutases by Bisphosphorylated Sugars in Heterotrophic Bacteria

Abstract (Expand)

Introduction: Phosphoglucomutases (PGM) are crucial for bacterial fitness, environmental survival, pathogenicity, and cell envelope stability, making them potential new targets for combating bacterial … infection and transmission. PGM functionality relies on initial phosphorylation by the activator glucose-1,6-bisphosphate (glucose-1,6-BP). While the origin of glucose-1,6-BP in vertebrates is well investigated, a bacterial glucose-1,6-BP synthase was only recently identified in the cyanobacterium Synechocystis. In this photoautotroph, a secondary PGM (SynPGM2) efficiently catalyzes glucose-1,6-BP synthesis from fructose-1,6-bisphosphate (fructose-1,6-BP) and glucose-1-phosphate or glucose-6-phosphate . A homologous PGM from the heterotrophic Bacteroides salyersiae, belonging to the same conserved domain subfamily (cd05800) as SynPGM2, exhibited similar activity, suggesting that bacterial glucose-1,6-BP synthesis is a feature of this specific subfamily. Methods: To investigate the specificity and regulation of various PGM enzymes from different heterotrophic bacteria, recombinant enzymes were purified and analyzed using enzymatic assays and HPLC-MS. Results: We demonstrate that glucose-1,6-BP synthesis extends beyond the cd5800 subfamily to the cd05801, cd05799, and cd03089 subfamilies. PGMs from Escherichia coli (cd05801 and cd03089), Enterococcus faecium (cd05799), Yersinia enterocolitica (cd05801), and Candidatus Gastranaerophilales (cd05800) catalyze the same fructose-1,6-BP-dependent synthesis reaction of glucose-1,6-BP as SynPGM2. Notably, fructose-1,6-BP, a known inhibitor of some PGM, does not inhibit these bacterial PGMs. Moreover, E. faecium PGM, belonging to the same subfamily as the mammalian glucose 1,6 BP synthase, efficiently catalyzes the mammalian-type 1,3-bisphosphoglycerate-dependent glucose 1,6-BP synthesis reaction. Conclusion: All investigated heterotrophic bacteria appear to use their primary PGM for both PGM activity and activator synthesis, suggesting a more versatile and less specialized role for PGMs in heterotrophic bacteria.

Authors: Janette T. Alford, Marina Borisova-Mayer, Christoph Mayer, Karl Forchhammer

Date Published: 16th Jul 2025

Publication Type: Journal Article

Powered by
 (v.1.18.1)
About FAIRDOMHub | Funding and Programmes | Credits | Terms & Conditions | Imprint | Cookie preferences
Copyright © 2008 - 2026 The University of Manchester and HITS gGmbH
Metadata is licensed under Creative Commons Attribution 4.0 International (CC-BY-4.0)