Evidence map›Paper›PMID 31271593›Full record

ArticleMemorias do Instituto Oswaldo Cruz2019

In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents.

Ana Claudia Manoel Von Trompowsky, Taline Ramos Conde, Renata Calil Lemos, Bruna Maria Cs Quaresma, Marcelly Cristina Sr Pitombeira, Alcione Silva de Carvalho, Núbia Boechat, Kelly Salomão, Solange Lisboa de Castro, Helena Pereira da Silva Zamith

Open access · diamondAbstract readEvaluation Study
In one paragraph

Article in Memorias do Instituto Oswaldo Cruz, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

2 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. 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

10 authors at 2 institutions in 1 country.

Ana Claudia Manoel Von TrompowskyFundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Controle de Qualidade em Saúde, Departamento de Farmacologia e Toxicologia, Rio de Janeiro, RJ, Brasil.
Taline Ramos CondeFundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Controle de Qualidade em Saúde, Departamento de Farmacologia e Toxicologia, Rio de Janeiro, RJ, Brasil.
Renata Calil LemosFundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Controle de Qualidade em Saúde, Departamento de Farmacologia e Toxicologia, Rio de Janeiro, RJ, Brasil.
Bruna Maria Cs QuaresmaUniversidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Programa de Pós-Graduação em Farmacologia e Química Medicinal, Rio de Janeiro, RJ, Brasil.
Marcelly Cristina Sr PitombeiraUniversidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Programa de Pós-Graduação em Farmacologia e Química Medicinal, Rio de Janeiro, RJ, Brasil.
Alcione Silva de CarvalhoFundação Oswaldo Cruz-Fiocruz, Instituto de Tecnologia em Fármacos, Departamento de Síntese de Fármacos, Farmanguinhos, Rio de Janeiro, RJ, Brasil.
Núbia BoechatFundação Oswaldo Cruz-Fiocruz, Instituto de Tecnologia em Fármacos, Departamento de Síntese de Fármacos, Farmanguinhos, Rio de Janeiro, RJ, Brasil.
Kelly SalomãoFundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil.
Solange Lisboa de CastroFundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil.
Helena Pereira da Silva ZamithFundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Controle de Qualidade em Saúde, Departamento de Farmacologia e Toxicologia, Rio de Janeiro, RJ, Brasil.ORCID http://orcid.org/0000-0002-8744-9673
Fundação Oswaldo Cruz · BRUniversidade Federal do Rio de Janeiro · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOnly benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3).

objectivesTo evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi.

methodsThe toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls.

findingsCompound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN

conclusionsCompound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1.

Indexed as

Blood CellsCell SurvivalComet AssayDNA DamageHumansMicronucleus TestsNifurtimoxNitroimidazolesReference ValuesReproducibility of ResultsThiadiazolesTime FactorsTrypanocidal AgentsTrypanosoma cruzibenzonidazolemegazolNifurtimoxNitroimidazolesThiadiazolesTrypanocidal Agents

Identifiers

PMID31271593
PMCPMC6598759
OpenAlexW2953688885

What OpenQuestion 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 OpenQuestion graph.