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Targeting trypanothione synthetase and Trypanothione reductase: development of common inhibitors to tackle Trypanosomatid disease

2025-08-11Journal article Open access
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dc.contributor.authorAugusto, André
dc.contributor.authorCosta, Inês
dc.contributor.authorConceição, Jaime
dc.contributor.authorCristiano, Maria de Lurdes
dc.date.accessioned2025-09-22T12:37:41Z
dc.date.available2025-09-22T12:37:41Z
dc.date.issued2025-08-11
dc.description.abstractNeglected Tropical Diseases (NTDs) encompass a range of disorders, including infectious diseases caused by viruses, bacteria, parasites, fungi, and toxins, mainly affecting underprivileged individuals in developing countries. Among the NTDs, those caused by parasites belonging to the Trypanosomatidae family are particularly impacting and require attention, since the lack of financial incentives has led to constraints on the development of novel drugs to tackle them effectively. To circumvent the minor advances in drug discovery in this area, academic research emerges as a crucial player, namely through the identification and validation of new drug targets, thereby contributing to the development of more efficient, safe, and less expensive therapies against Trypanosomatidae infections. Noteworthy, this is a matter of utmost urgency since these diseases are endemic in countries with low socioeconomic standards. This review provides a comprehensive understanding of the current paradigm of NTDs caused by parasites belonging to the Trypanosomatidae family, addressing the ongoing limitations and challenges associated to the current chemotherapy solutions for these diseases and discussing the opportunities unravelled by recent research that led to the identification of new biomolecular targets that are common to Trypanosomatidae parasites. Among these, the unique properties of Trypanothione Synthetase (TryS) and Trypanothione Reductase (TryR), two key protozoan enzymes that are essential for the survival of Trypanosoma and Leishmania parasites, will be emphasised. In addition to a critical analysis of the latest advances in the discovery of novel molecules capable of inhibiting TryS and TryR, the possibility of dual targeting through a combination of TryS and TryR inhibitors will be addressed.eng
dc.description.sponsorshipSFRH/BD/08242/2020
dc.identifier.doi10.3390/ph18081182
dc.identifier.issn1424-8247
dc.identifier.urihttp://hdl.handle.net/10400.1/27720
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relationAlgarve Centre for Marine Sciences
dc.relationAlgarve Centre for Marine Sciences
dc.relationCentre for Marine and Environmental Research
dc.relation.ispartofPharmaceuticals
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectNeglected tropical diseases
dc.subjectLeishmaniases
dc.subjectTrypanosomiasis
dc.subjectTrypanothione reductase
dc.subjectTrypanothione synthetase
dc.subjectInhibitors
dc.titleTargeting trypanothione synthetase and Trypanothione reductase: development of common inhibitors to tackle Trypanosomatid diseaseeng
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleCentre for Marine and Environmental Research
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0101%2F2020/PT
oaire.citation.issue8
oaire.citation.startPage1182
oaire.citation.titlePharmaceuticals
oaire.citation.volume18
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameAugusto
person.familyNameCosta
person.familyNameConceição
person.familyNameCristiano
person.givenNameAndré
person.givenNameInês
person.givenNameJaime
person.givenNameMaria de Lurdes
person.identifier.ciencia-idE411-6006-5A01
person.identifier.orcid0009-0001-7676-4774
person.identifier.orcid0000-0003-2711-5441
person.identifier.orcid0000-0002-6201-3662
person.identifier.orcid0000-0002-9447-2855
person.identifier.ridG-2345-2012
person.identifier.scopus-author-id9238724800
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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