Evidence map›Paper›PMID 34357687›Full record

ArticleChemMedChem2021

Direct, Late-Stage Mono-N-arylation of Pentamidine: Method Development, Mechanistic Insight, and Expedient Access to Novel Antiparastitics against Diamidine-Resistant Parasites.

Jack Robertson, Marzuq A Ungogo, Mustafa M Aldfer, Leandro Lemgruber, Fergus S McWhinnie, Bela E Bode, Katherine L Jones, Allan J B Watson, Harry P de Koning, Glenn A Burley

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Functional Studies of Kinetoplastid Transporters.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  2. Cytological profiling of trypanocidal principles fromPhytomedicine plus : international journal of phytotherapy and phytopharmacology · 2025
    Article
  3. Drug resistance in animal trypanosomiases: Epidemiology, mechanisms and control strategies.International journal for parasitology. Drugs and drug resistance · 2024
    Review
  4. Synthesis and Biophysical and Biological Studies ofJournal of medicinal chemistry · 2023
    Article
  5. 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.

Jack RobertsonDepartment of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK.
Marzuq A UngogoInstitute of Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Mustafa M AldferInstitute of Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Leandro LemgruberGlasgow Imaging Facility, Institute of Infection, Immunity, and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Fergus S McWhinnieDepartment of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK.
Bela E BodeEaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
Katherine L JonesGlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
Allan J B WatsonEaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
Harry P de KoningInstitute of Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Glenn A BurleyDepartment of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK.

Funding

Engineering and Physical Sciences Research CouncilGlaxoSmithKlinegovernment of LibyaPetroleum Technology Development Fund
6 · The paper itself

Abstract

A selective mono-N-arylation strategy of amidines under Chan-Lam conditions is described. During the reaction optimization phase, the isolation of a mononuclear Cu(II) complex provided unique mechanistic insight into the operation of Chan-Lam mono-N-arylation. The scope of the process is demonstrated, and then applied to access the first mono-N-arylated analogues of pentamidine. Sub-micromolar activity against kinetoplastid parasites was observed for several analogues with no cross-resistance in pentamidine and diminazene-resistant trypanosome strains and against Leishmania mexicana. A fluorescent mono-N-arylated pentamidine analogue revealed rapid cellular uptake, accumulating in parasite nuclei and the kinetoplasts. The DNA binding capability of the mono-N-arylated pentamidine series was confirmed by UV-melt measurements using AT-rich DNA. This work highlights the potential to use Chan-Lam mono-N-arylation to develop therapeutic leads against diamidine-resistant trypanosomiasis and leishmaniasis.

Indexed as

Drug DevelopmentAmidinesAntiparasitic AgentsDose-Response Relationship, DrugDrug ResistanceLeishmania mexicanaMolecular StructureParasitic Sensitivity TestsPentamidineStructure-Activity RelationshipAmidinesAntiparasitic AgentsPentamidineamidineantiparasiticsarylationcoppermedicinal chemistry

Identifiers

PMID34357687
PMCPMC9291547

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.