Evidence map›Paper›PMID 33617566›Full record

ArticlePLoS neglected tropical diseases2021

2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling.

Rafael Augusto Alves Ferreira, Celso de Oliveira Rezende Junior, Pablo David Grigol Martinez, Paul John Koovits, Bruna Miranda Soares, Leonardo L G Ferreira, Simone Michelan-Duarte, Rafael Consolin Chelucci, Adriano D Andricopulo, Mariana K Galuppo and 8 more

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
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

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Current leishmaniasis drug discovery.RSC medicinal chemistry · 2022
    Review
  9. Article
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

18 authors at 4 institutions in 3 countries.

Rafael Augusto Alves FerreiraInstitute of Chemistry, University of Campinas (UNICAMP), Campinas-SP, Brazil.
Celso de Oliveira Rezende JuniorInstitute of Chemistry, University of Campinas (UNICAMP), Campinas-SP, Brazil.ORCID 0000-0003-1402-2035
Pablo David Grigol MartinezInstitute of Chemistry, University of Campinas (UNICAMP), Campinas-SP, Brazil.ORCID 0000-0003-1940-696X
Paul John KoovitsInstitute of Chemistry, University of Campinas (UNICAMP), Campinas-SP, Brazil.ORCID 0000-0002-8435-9437
Bruna Miranda SoaresInstitute of Chemistry, University of Campinas (UNICAMP), Campinas-SP, Brazil.
Leonardo L G FerreiraLaboratory of Medicinal and Computational Chemistry, Physics Institute of São Carlos, University of São Paulo (USP), São Carlos-SP, Brazil.ORCID 0000-0002-6947-0639
Simone Michelan-DuarteLaboratory of Medicinal and Computational Chemistry, Physics Institute of São Carlos, University of São Paulo (USP), São Carlos-SP, Brazil.
Rafael Consolin ChelucciLaboratory of Medicinal and Computational Chemistry, Physics Institute of São Carlos, University of São Paulo (USP), São Carlos-SP, Brazil.
Adriano D AndricopuloLaboratory of Medicinal and Computational Chemistry, Physics Institute of São Carlos, University of São Paulo (USP), São Carlos-SP, Brazil.ORCID 0000-0002-0457-818X
Mariana K GaluppoDepartment of Parasitology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo-SP, Brazil.
Silvia R B UlianaDepartment of Parasitology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo-SP, Brazil.ORCID 0000-0002-8070-3704
An MatheeussenLaboratory of Microbiology, Parasitology and Hygiene (LMPH), Antwerpen, Belgium.ORCID 0000-0002-7507-1634
Guy CaljonLaboratory of Microbiology, Parasitology and Hygiene (LMPH), Antwerpen, Belgium.ORCID 0000-0002-4870-3202
Louis MaesLaboratory of Microbiology, Parasitology and Hygiene (LMPH), Antwerpen, Belgium.ORCID 0000-0002-2324-9509
Simon CampbellDrugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
Jadel M KratzDrugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.ORCID 0000-0002-7681-8234
Charles E MowbrayDrugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.ORCID 0000-0003-3538-8116
Luiz Carlos DiasInstitute of Chemistry, University of Campinas (UNICAMP), Campinas-SP, Brazil.ORCID 0000-0003-0628-9928
Universidade de São Paulo · BRUniversidade Estadual de Campinas (UNICAMP) · BRDrugs for Neglected Diseases Initiative · CHProvincial Institute for Hygiene · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum as part of an optimization program; a compound was found with a 2-aminobenzimidazole functionality presenting moderate potency, low metabolic stability and high lipophilicity. Several rounds of synthesis were performed to incorporate chemical groups capable of reducing lipophilicity and clearance, leading to the identification of compounds that are active against different parasite strains and have improved in vitro properties. As a result of this optimization program, a group of compounds was further tested in anticipation of in vivo evaluation. In vivo tests were carried out with compounds 29 (L. infantum IC50: 4.1 μM) and 39 (L. infantum IC50: 0.5 μM) in an acute L. infantum VL mouse model, which showed problems of poor exposure and lack of efficacy, despite the good in vitro potency.

Indexed as

Drug DiscoveryAnimalsAntiprotozoal AgentsBenzimidazolesDisease Models, AnimalFemaleHumansLeishmania infantumLeishmaniasisMiceMice, Inbred BALB CMicrosomes, Liver2-aminobenzimidazoleAntiprotozoal AgentsBenzimidazoles

Identifiers

PMID33617566
PMCPMC7932521
OpenAlexW3131252450

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.