Evidence map›Paper›PMID 36543032›Full record

ArticleEuropean journal of medicinal chemistry2023

Isoform selectivities of novel 4-hydroxycoumarin imines as inhibitors of myosin II.

Joshua D Smith, Jhonnathan Brawley, Kate C Bordenave, Ryan K Olsen, Amarawan Intasiri, Christine R Cremo, Thomas W Bell

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

Article in European journal of medicinal chemistry, 2023. 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
0.8field-weighted citation impact, top 25% 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, 5 citations in OpenAlex.

  1. Review
  2. 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

7 authors at 1 institution in 1 country.

Joshua D SmithDepartment of Pharmacology, University of Nevada, School of Medicine, Reno, NV, 89557-0318, USA.
Jhonnathan BrawleyDepartment of Chemistry, University of Nevada, Reno, NV, 89557-0216, USA.
Kate C BordenaveDepartment of Pharmacology, University of Nevada, School of Medicine, Reno, NV, 89557-0318, USA.
Ryan K OlsenDepartment of Chemistry, University of Nevada, Reno, NV, 89557-0216, USA.
Amarawan IntasiriDepartment of Chemistry, University of Nevada, Reno, NV, 89557-0216, USA.
Christine R CremoDepartment of Pharmacology, University of Nevada, School of Medicine, Reno, NV, 89557-0318, USA. Electronic address: cremo@unr.edu.
Thomas W BellDepartment of Chemistry, University of Nevada, Reno, NV, 89557-0216, USA. Electronic address: twb@unr.edu.
University of Nevada, Reno · US

Funding

Mechanochemistry of Myosin II FilamentsR01AR071405 · NIAMS · UNIVERSITY OF NEVADA RENO · PI BAKER, JONATHAN E., CREMO, CHRISTINE R · 2017 to 2021
$2.1M
Development of a Novel Inhibitor for Hepatitis BR21AI154254 · NIAID · UNIVERSITY OF NEVADA RENO · PI BELL, THOMAS W. · 2020 to 2021
$385k
NIAID NIH HHS R21 AI154254NIAMS NIH HHS R01 AR071405
6 · The paper itself

Abstract

Muscle myosin inhibition could be used to treat many medical conditions involving hypercontractile states, including muscle spasticity, chronic musculoskeletal pain, and hypertrophic cardiomyopathy. A series of 13 advanced analogs of 3-(N-butylethanimidoyl)ethyl)-4-hydroxy-2H-chromen-2-one (BHC) were synthesized to explore extended imine nitrogen side chains and compare aldimines vs. ketimines. None of the new analogs inhibit nonmuscle myosin in a cytokinesis assay. ATPase structure-activity relationships reveal that selectivity for cardiac vs. skeletal myosin can be tuned with subtle structural changes. None of the compounds inhibited smooth muscle myosin II. Docking the compounds to homology models of cardiac and skeletal myosin II gave rationales for the effects of side arm length on inhibition selectivity and for cardiac vs. skeletal myosin. Properties including solubility, stability and toxicity, suggest that certain BHC analogs may be useful as candidates for preclinical studies or as lead compounds for advanced candidates for drugs with cardiac or skeletal muscle myosin selectivity.

Indexed as

4-HydroxycoumarinsMyosin Type IIAdenosine TriphosphatasesMyosinsProtein Isoforms4-HydroxycoumarinsAdenosine TriphosphatasesMyosinsMyosin Type IIProtein IsoformsDockingHomology modelHydroxyquinoline imineMyosin inhibitorSelectivityStructure-activity relationships

Identifiers

PMID36543032
PMCPMC9889102
OpenAlexW4312052893

What OpenQuestion holds

Textmetadata
LicenceTDM
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.