ArticleAntimicrobial agents and chemotherapy2010
Novel arylimidamides for treatment of visceral leishmaniasis.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Novel amidines and analogues as promising agents against intracellular parasites: a systematic review.Parasitology · 2013Pooled it
- Article
- CYP5122A1 encodes an essential sterol C4-methyl oxidase in Leishmania donovani and determines the antileishmanial activity of antifungal azoles.Nature communications · 2024Article
- Molecular Characterization of Sterol C4-Methyl Oxidase inInternational journal of molecular sciences · 2024Article
- Synthesis and Biophysical and Biological Studies ofJournal of medicinal chemistry · 2023Article
- Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker.ACS infectious diseases · 2021Article
- Acarbose presents in vitro and in vivo antileishmanial activity against Leishmania infantum and is a promising therapeutic candidate against visceral leishmaniasis.Medical microbiology and immunology · 2021Article
- Article
- Antileishmanial Efficacy and Pharmacokinetics of DB766-Azole Combinations.Antimicrobial agents and chemotherapy · 2018Article
- Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery.Antimicrobial agents and chemotherapy · 2017Article
- Identification of a Hit Series of Antileishmanial Compounds through the Use of Mixture-Based Libraries.ACS medicinal chemistry letters · 2017Article
- Phenotypic evaluation and in silico ADMET properties of novel arylimidamides in acute mouse models ofDrug design, development and therapy · 2017Article
- Drug target identification in protozoan parasites.Expert opinion on drug discovery · 2016Review
- Synthesis of novel amide and urea derivatives of thiazol-2-ethylamines and their activity against Trypanosoma brucei rhodesiense.Bioorganic & medicinal chemistry · 2016Article
- Synthesis and pharmacological evaluation of mono-arylimidamides as antileishmanial agents.Bioorganic & medicinal chemistry letters · 2016Article
- Bis-benzimidazole hits against Naegleria fowleri discovered with new high-throughput screens.Antimicrobial agents and chemotherapy · 2015Article
- Unveiling the effects of berenil, a DNA-binding drug, on Trypanosoma cruzi: implications for kDNA ultrastructure and replication.Parasitology research · 2015Article
- Studies on the antileishmanial mechanism of action of the arylimidamide DB766: azole interactions and role of CYP5122A1.Antimicrobial agents and chemotherapy · 2014Article
- In vitro and in vivo studies of the biological activity of novel arylimidamides against Trypanosoma cruzi.Antimicrobial agents and chemotherapy · 2014Article
- Pharmacokinetic comparison to determine the mechanisms underlying the differential efficacies of cationic diamidines against first- and second-stage human African trypanosomiasis.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Arylimidamides (AIAs) represent a new class of molecules that exhibit potent antileishmanial activity (50% inhibitory concentration [IC(50)], <1 microM) against both Leishmania donovani axenic amastigotes and intracellular Leishmania, the causative agent for human visceral leishmaniasis (VL). A systematic lead discovery program was employed to characterize in vitro and in vivo antileishmanial activities, pharmacokinetics, mutagenicities, and toxicities of two novel AIAs, DB745 and DB766. They were exceptionally active (IC(50) < or = 0.12 microM) against intracellular L. donovani, Leishmania amazonensis, and Leishmania major and did not exhibit mutagenicity in an Ames screen. DB745 and DB766, given orally, produced a dose-dependent inhibition of liver parasitemia in two efficacy models, L. donovani-infected mice and hamsters. Most notably, DB766 (100 mg/kg of body weight/day for 5 days) reduced liver parasitemia in mice and hamsters by 71% and 89%, respectively. Marked reduction of parasitemia in the spleen (79%) and bone marrow (92%) of hamsters was also observed. Furthermore, these compounds distributed to target tissues (liver and spleen) and had a moderate oral bioavailability (up to 25%), a large volume of distribution, and an elimination half-life ranging from 1 to 2 days in mice. In a repeat-dose toxicity study of mice, there was no indication of liver or kidney toxicity for DB766 from serum chemistries, although mild hepatic cell eosinophilia, hypertrophy, and fatty changes were noted. These results demonstrated that arylimidamides are a promising class of molecules that possess good antileishmanial activity and desirable pharmacokinetics and should be considered for further preclinical development as an oral treatment for VL.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.