Evidence map›Paper›PMID 25778768›Full record

ArticleBioorganic & medicinal chemistry2015

Base-modified thymidines capable of terminating DNA synthesis are novel bioactive compounds with activity in cancer cells.

Kayla M Borland, Safnas F AbdulSalam, Morwena J Solivio, Matthew P Burke, Patrick R Wolfkiel, Sean M Lawson, Courtney A Stockman, Joel M Andersen, Skyler Smith, Julia N Tolstolutskaya and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

1 citing paper in PubMed, 7 citations in OpenAlex.

  1. 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

14 authors at 1 institution in 1 country.

Kayla M BorlandDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Safnas F AbdulSalamDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Morwena J SolivioDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Matthew P BurkeDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Patrick R WolfkielDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Sean M LawsonDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Courtney A StockmanDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Joel M AndersenDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Skyler SmithDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Julia N TolstolutskayaDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Purujit N GurjarDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Aron P BerczDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Edward J MerinoDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA.
Vladislav A LitoshDepartment of Chemistry, University of Cincinnati, 301 Clifton Ct. ML 0172, Cincinnati, OH 45221-0172, USA. Electronic address: Vladislav.Litosh@uc.edu.
University of Cincinnati · US

Funding

LCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., KISSELA, BRETT M · 2015 to 2024
$37.5M
Conferring in vivo metabolic resistance to a highly selective anti-AML agentR21CA185370 · NCI · UNIVERSITY OF CINCINNATI · PI MERINO, EDWARD J · 2014 to 2015
$370k
NCATS NIH HHS UL1 TR001425NCI NIH HHS R21 CA185370NCI NIH HHS R21CA185370
6 · The paper itself

Abstract

Current FDA-approved chemotherapeutic antimetabolites elicit severe side effects that warrant their improvement; therefore, we designed compounds with mechanisms of action focusing on inhibiting DNA replication rather than targeting multiple pathways. We previously discovered that 5-(α-substituted-2-nitrobenzyloxy)methyluridine-5'-triphosphates were exquisite DNA synthesis terminators; therefore, we synthesized a library of 35 thymidine analogs and evaluated their activity using an MTT cell viability assay of MCF7 breast cancer cells chosen for their vulnerability to these nucleoside derivatives. Compound 3a, having an α-tert-butyl-2-nitro-4-(phenyl)alkynylbenzyloxy group, showed an IC50 of 9±1μM. The compound is more selective for cancer cells than for fibroblast cells compared with 5-fluorouracil. Treatment of MCF7 cells with 3a elicits the DNA damage response as indicated by phosphorylation of γ-H2A. A primer extension assay of the 5'-triphosphate of 3a revealed that 3aTP is more likely to inhibit DNA polymerase than to lead to termination events upon incorporation into the DNA replication fork.

Indexed as

Antimetabolites, AntineoplasticBreast NeoplasmsDNA ReplicationFemaleHumansMCF-7 CellsNucleic Acid Synthesis InhibitorsThymidineAntimetabolites, AntineoplasticNucleic Acid Synthesis InhibitorsThymidineAntimetabolitesCancerChemotherapeuticsDNA terminationNucleosidesNucleotides

Identifiers

PMID25778768
PMCPMC4380762
OpenAlexW1988032473

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.