Assessment of the Binding Affinity of Covalent Inhibitors of Cruzain and Cathepsin L Using Relative Binding Free Energy.

Yan Carvalho Magno, Luiz Fernando Barbosa, Maycon Vinicius Damasceno de Oliveira, Jerônimo Lameira, Carlos A Montanari

Abstract read

In one paragraph

Article in ChemMedChem, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yan Carvalho MagnoLaboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, Pará, Brazil.ORCID https://orcid.org/0009-0000-7419-1864

Luiz Fernando BarbosaMedicinal and Biological Chemistry Group, São Carlos Institute of Chemistry, University of São Paulo, São Carlos, São Paulo, Brazil.ORCID https://orcid.org/0000-0002-3212-4513

Maycon Vinicius Damasceno de OliveiraLaboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, Pará, Brazil.ORCID https://orcid.org/0000-0003-2263-2124

Jerônimo LameiraLaboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, Pará, Brazil.ORCID https://orcid.org/0000-0001-7270-1517

Carlos A MontanariMedicinal and Biological Chemistry Group, São Carlos Institute of Chemistry, University of São Paulo, São Carlos, São Paulo, Brazil.ORCID https://orcid.org/0000-0002-4963-0316

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 305182/2021-8Conselho Nacional de Desenvolvimento Científico e Tecnológico 402311/2024-8Conselho Nacional de Desenvolvimento Científico e Tecnológico 404652/2025-5

6 · The paper itself

Abstract

Cysteine proteases are recognized as relevant therapeutic targets in both parasitic diseases and cancer due to their essential biological functions. Among these enzymes, cruzain from Trypanosoma cruzi is an important molecular target for the treatment of Chagas disease. Likewise, human cathepsin L (hCatL) is a potential target for anticancer drug development. Both enzymes share conserved catalytic features, particularly the cysteine-histidine catalytic dyad, which enables interaction with nitrile-based reversible covalent inhibitors. Here, six nitrile-derived inhibitors (Neq1171.1, Neq1172.1, Neq1181.1, Neq1182.1, Neq1268, and Neq1276) had their cruzain and hCatL inhibition constants, K

Indexed as

Cathepsin LCysteine EndopeptidasesCysteine Proteinase InhibitorsNitrilesProtozoan ProteinsBinding SitesHumansMolecular Dynamics SimulationMolecular StructureProtein BindingStructure-Activity RelationshipThermodynamicsTrypanosoma cruziCathepsin Lcruzain, Trypanosoma cruziCysteine EndopeptidasesCysteine Proteinase InhibitorsNitrilesProtozoan Proteinsbiochemistrycathepsin LChagas diseasechemistrycovalent bondcysteine proteasemolecular dynamicsnitrileprotease

Identifiers

PMID42802308

DOI10.1002/cmdc.70508

PMCPMC13616992

What OpenQuestion holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.