Evidence map›Paper›PMID 32617557›Full record

ArticleThe Journal of antimicrobial chemotherapy2020

Efficacy, metabolism and pharmacokinetics of Ro 15-5458, a forgotten schistosomicidal 9-acridanone hydrazone.

Alexandra Probst, Cécile Häberli, Dionicio Siegel, Jianbo Huang, Seth Vigneron, Anh P Ta, Danielle E Skinner, Nelly El-Sakkary, Jeremiah D Momper, Jon Gangoiti and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 41% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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

15 authors at 4 institutions in 3 countries.

Alexandra ProbstDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, PO Box, CH-4002, Basel, Switzerland.
Cécile HäberliDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, PO Box, CH-4002, Basel, Switzerland.
Dionicio SiegelCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Jianbo HuangCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Seth VigneronCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Anh P TaCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Danielle E SkinnerCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Nelly El-SakkaryCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Jeremiah D MomperCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Jon GangoitiBiochemical Genetics and Metabolomics Laboratory, Department of Pediatrics, School of Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Yuxiang DongCollege of Pharmacy, University of Nebraska Medical Center, 986125 Nebraska Medical Center, Omaha, NE, USA.
Jonathan L VennerstromCollege of Pharmacy, University of Nebraska Medical Center, 986125 Nebraska Medical Center, Omaha, NE, USA.
Susan A CharmanCentre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Conor R CaffreyCenter for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Jennifer KeiserDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, PO Box, CH-4002, Basel, Switzerland.
University of California San Diego · USSwiss Tropical and Public Health Institute · CHNebraska Medical Center · USMonash University · AU

Funding

Optimization of Antischistosomal ChemotypesR01AI116723 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI VENNERSTROM, JONATHAN L · 2015 to 2024
$6.2M
Defining the death transcriptome of Schistosoma mansoni to construct a molecular drug screenR21AI126296 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CAFFREY, CONOR · 2017 to 2018
$415k
NIAID NIH HHS HHSN272201000005CNIAID NIH HHS HHSN272201000005INIAID NIH HHS HHSN272201700014CNIAID NIH HHS R01 AI116723NIAID NIH HHS R21 AI126296
6 · The paper itself

Abstract

backgroundTreatment of schistosomiasis, a neglected disease, relies on just one partially effective drug, praziquantel. We revisited the 9-acridanone hydrazone, Ro 15-5458, a largely forgotten antischistosomal lead compound.

methodsRo 15-5458 was evaluated in juvenile and adult Schistosoma mansoni-infected mice. We studied dose-response, hepatic shift and stage specificity. The metabolic stability of Ro 15-5458 was measured in the presence of human and mouse liver microsomes, and human hepatocytes; the latter also served to identify metabolites. Pharmacokinetic parameters were measured in naive mice. The efficacy of Ro 15-5458 was also assessed in S. haematobium-infected hamsters and S. japonicum-infected mice.

resultsRo 15-5458 had single-dose ED50 values of 15 and 5.3 mg/kg in mice harbouring juvenile and adult S. mansoni infections, respectively. An ED50 value of 17 mg/kg was measured in S. haematobium-infected hamsters; however, the compound was inactive at up to 100 mg/kg in S. japonicum-infected mice. The drug-induced hepatic shift occurred between 48 and 66 h post treatment. A single oral dose of 50 mg/kg of Ro 15-5458 had high activity against all tested S. mansoni stages (1-, 7-, 14-, 21- and 49-day-old). In vitro, human hepatocytes produced N-desethyl and glucuronide metabolites; otherwise Ro 15-5458 was metabolically stable in the presence of microsomes or whole hepatocytes. The maximum plasma concentration was approximately 8.13 μg/mL 3 h after a 50 mg/kg oral dose and the half-life was approximately 4.9 h.

conclusionsRo 15-5458 has high activity against S. mansoni and S. haematobium, yet lacks activity against S. japonicum, which is striking. This will require further investigation, as a broad-spectrum antischistosomal drug is desirable.

Indexed as

Schistosomiasis mansoniSchistosomicidesAcridinesAnimalsCricetinaeHydrazonesMiceSchistosoma mansoniAcridinesHydrazonesRo 15-5458Schistosomicides

Identifiers

PMID32617557
PMCPMC7556815
OpenAlexW3038627416

What OpenQuestion holds

Textmetadata
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Registered trials

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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.