Publications

What is a Publication?
14 Publications visible to you, out of a total of 14
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

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

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

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

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

Environmental impacts of drugs against parasitic vector-borne diseases and the need to integrate sustainability into their development and use

Abstract (Expand)

<ns3:p> Background The current scientific discourse on environmental impacts of veterinary medicines mostly focuses on ectoparasiticides. Meanwhile, the environmental impacts of widely prescribed …of widely prescribed drugs for the treatment of human and animal parasitic vector-borne diseases (PVBD) remain largely unexplored. There is thus a need for evidence-based information to support guidelines and protocols for sustainable One Health PVBD drug development and use, while promoting greener research practices. Here, we reflect on the potential environmental impacts of PVBD drugs in current use, and the environmental impact of our research practices for developing new antiparasitics. Methods We conducted a survey of the membership of the “One Health drugs against parasitic vector borne diseases in Europe and beyond” Cooperation in Science and Technology (COST) Action 21111 (OneHealth <ns3:italic>drugs</ns3:italic> ) to assess the current appreciation of sustainable drug design concepts and the extent to which One Health and sustainability principles are integrated into PVBD drug discovery and development. The survey also explored which human, technical, and funding resources are currently used in Europe and neighbouring countries in PVBD drugs research. Results The survey was conducted and analysed by OneHealth <ns3:italic>drugs</ns3:italic> and garnered 89 respondents, representing a response rate of 66% from 32 countries, predominantly European. 87% of participating collaborators worked in Academia; research groups were small (60% with 1–4 researchers) and mostly consist of few researchers, mostly at early career stages (63% <35 years old). Collaborations were mostly between academics, and 60% collaborated with non-European researchers, while funding was mostly from national governments. Motivation for greener research practices was high but there was as yet low implementation of green strategies or the incorporation of ecotoxicological test in drug development workflows, due to cost and unfamiliarity. Conclusions We highlight the need for early-ecotoxicological testing of new drug candidates and suggest best practices as we move towards standardized protocols in developing safe and efficacious PVBD drugs. </ns3:p>

Authors: Clara M. Lima, Elisa Uliassi, Eli S.J. Thoré, Michael G. Bertram, Luis Cardoso, Anabela Cordeiro da Silva, Maria Paola Costi, Harry P. de Koning

Date Published: 4th Nov 2024

Publication Type: Journal Article

Identification of Innovative Folate Inhibitors Leveraging the Amino Dihydrotriazine Motif from Cycloguanil for Their Potential as Anti-<i>Trypanosoma brucei</i> Agents

Abstract

Not specified

Authors: Valeria Francesconi, Marco Rizzo, Cecilia Pozzi, Lorenzo Tagliazucchi, Claude U. Konchie Simo, Giulia Saporito, Giacomo Landi, Stefano Mangani, Anna Carbone, Silvia Schenone, Nuno Santarém, Joana Tavares, Anabela Cordeiro-da-Silva, Maria Paola Costi, Michele Tonelli

Date Published: 2nd Jul 2024

Publication Type: Journal Article

One Health

Abstract

Not specified

Authors: Michael G. Bertram, Maria Paola Costi, Eli S.J. Thoré, Tara Sabo-Attwood, Bryan W. Brooks

Date Published: 1st Jun 2024

Publication Type: Journal Article

Assessing Environmental Risks during the Drug Development Process for Parasitic Vector-Borne Diseases: A Critical Reflection

Abstract

Not specified

Authors: Kayhan Ilbeigi, Carlos Barata, João Barbosa, Michael G. Bertram, Guy Caljon, Maria Paola Costi, Alexandra Kroll, Luigi Margiotta-Casaluci, Eli S.J. Thoré, Mirco Bundschuh

Date Published: 27th Mar 2024

Publication Type: Journal Article

The discovery of aryl-2-nitroethyl triamino pyrimidines as anti-Trypanosoma brucei agents

Abstract

Not specified

Authors: Pasquale Linciano, Cecilia Pozzi, Giusy Tassone, Giacomo Landi, Stefano Mangani, Matteo Santucci, Rosaria Luciani, Stefania Ferrari, Nuno Santarem, Lorenzo Tagliazucchi, Anabela Cordeiro-da-Silva, Michele Tonelli, Donatella Tondi, Laura Bertarini, Sheraz Gul, Gesa Witt, Carolina B. Moraes, Luca Costantino, Maria Paola Costi

Date Published: 2024

Publication Type: Journal Article

High-Throughput Phenotypic Screening and Machine Learning Methods Enabled the Selection of Broad-Spectrum Low-Toxicity Antitrypanosomatidic Agents

Abstract

Not specified

Authors: Pasquale Linciano, Antonio Quotadamo, Rosaria Luciani, Matteo Santucci, Kimberley M. Zorn, Daniel H. Foil, Thomas R. Lane, Anabela Cordeiro da Silva, Nuno Santarem, Carolina B Moraes, Lucio Freitas-Junior, Ulrike Wittig, Wolfgang Mueller, Michele Tonelli, Stefania Ferrari, Alberto Venturelli, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Jeanette Reinshagen, Sean Ekins, Maria Paola Costi

Date Published: 3rd Nov 2023

Publication Type: Journal Article

Call for Papers: One Health and Vector-Borne Parasitic Diseases

Abstract

Not specified

Authors: Maria P. Costi, Anabela Cordeiro-da-Silva

Date Published: 23rd Jul 2023

Publication Type: Journal Article

Label-Free Mass Spectrometry Proteomics Reveals Different Pathways Modulated in THP-1 Cells Infected with Therapeutic Failure and Drug Resistance <i>Leishmania infantum</i> Clinical Isolates

Abstract

Not specified

Authors: Lorenzo Tagliazucchi, Ana Perea-Martinez, Greta Fiorini, José Ignacio Manzano, Filippo Genovese, Raquel García-Hernández, Diego Pinetti, Francisco Gamarro, Maria Paola Costi

Date Published: 10th Feb 2023

Publication Type: Journal Article

Current Treatments to Control African Trypanosomiasis and One Health Perspective

Abstract (Expand)

Human African Trypanosomiasis (HAT, sleeping sickness) and Animal African Trypanosomiasis (AAT) are neglected tropical diseases generally caused by the same etiological agent, Trypanosoma brucei. Despite … important advances in the reduction or disappearance of HAT cases, AAT represents a risky reservoir of the infections. There is a strong need to control AAT, as is claimed by the European Commission in a recent document on the reservation of antimicrobials for human use. Control of AAT is considered part of the One Health approach established by the FAO program against African Trypanosomiasis. Under the umbrella of the One Health concepts, in this work, by analyzing the pharmacological properties of the therapeutic options against Trypanosoma brucei spp., we underline the need for clearer and more defined guidelines in the employment of drugs designed for HAT and AAT. Essential requirements are addressed to meet the challenge of drug use and drug resistance development. This approach shall avoid inter-species cross-resistance phenomena and retain drugs therapeutic activity.

Authors: Alberto Venturelli, Lorenzo Tagliazucchi, Clara Lima, Federica Venuti, Giulia Malpezzi, George E. Magoulas, Nuno Santarem, Theodora Calogeropoulou, Anabela Cordeiro-da-Silva, Maria Paola Costi

Date Published: 27th Jun 2022

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)