Evidence map›Paper›PMID 39437789›Full record

ArticleCell chemical biology2024

Quinoline-based compounds can inhibit diverse enzymes that act on DNA.

Jujun Zhou, Qin Chen, Ren Ren, Jie Yang, Bigang Liu, John R Horton, Caleb Chang, Chuxuan Li, Leora Maksoud, Yifei Yang and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2024. 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
–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

3 citing papers in PubMed.

  1. Legacy 4(1ACS infectious diseases · 2026
    Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Jujun ZhouDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Qin ChenDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ren RenDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jie YangDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Bigang LiuDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
John R HortonDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Caleb ChangDepartment of Biosciences, Rice University, Houston, TX 77005, USA.
Chuxuan LiDepartment of Biosciences, Rice University, Houston, TX 77005, USA.
Leora MaksoudDepartment of Biosciences, Rice University, Houston, TX 77005, USA.
Yifei YangDepartment of Biosciences, Rice University, Houston, TX 77005, USA.
Dante RotiliDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Abhinav K JainDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xing ZhangDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Robert M BlumenthalDepartment of Medical Microbiology and Immunology, and Program in Bioinformatics, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Taiping ChenDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yang GaoDepartment of Biosciences, Rice University, Houston, TX 77005, USA.
Sergio ValenteDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Antonello MaiDepartment of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Pasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Xiaodong ChengDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: xcheng5@mdanderson.org.

Funding

Pathology CoreP50CA254897 · NCI · CORIELL INSTITUTE FOR MEDICAL RESEARCH · PI ISSA, JEAN-PIERRE J. · 2021 to 2025
$11.9M
Epigenetic regulations of DNA and histone methylation and deMethylation: Structures and MechanismsR35GM134744 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Xiaodong Cheng · 2020 to 2026
$4.5M
Preclinical studies of non-nucleoside DNMT3A/3B inhibitorsR21CA277152 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, TAIPING, CHENG, XIAODONG · 2024 to 2025
$417k
NCI NIH HHS P50 CA254897NCI NIH HHS R21 CA277152NIGMS NIH HHS R35 GM134744
6 · The paper itself

Abstract

DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a key epigenetic process. Developing non-nucleoside inhibitors to cause DNA hypomethylation is crucial for treating various conditions without the toxicities associated with existing cytidine-based hypomethylating agents. This study characterized fifteen quinoline-based analogs, particularly compounds with additions like a methylamine (9) or methylpiperazine (11), which demonstrate similar low micromolar inhibitory potency against human DNMT1 and Clostridioides difficile CamA. These compounds (9 and 11) intercalate into CamA-bound DNA via the minor groove, causing a conformational shift that moves the catalytic domain away from the DNA. This study adds to the limited examples of DNA methyltransferases being inhibited by non-nucleotide compounds through DNA intercalation. Additionally, some quinoline-based analogs inhibit other DNA-interacting enzymes, such as polymerases and base excision repair glycosylases. Finally, compound 11 elicits DNA damage response via p53 activation in cancer cells.

Indexed as

DNADNA (Cytosine-5-)-Methyltransferase 1Enzyme InhibitorsQuinolinesBacterial ProteinsClostridioides difficileDNA MethylationHumansMolecular StructureStructure-Activity RelationshipBacterial ProteinsDNADNA (Cytosine-5-)-Methyltransferase 1DNMT1 protein, humanEnzyme InhibitorsquinolineQuinolinesBER glycosylasesDNA adeinine methyltransferasesDNA cytosine methyltransferasesDNA hypomethylating agentsDNA intercalationDNA/RNA polymerasesnon-nucleoside compoundp53 responsepan inhibitors of DNA-acting enzymesquinoline-based analogs

Identifiers

PMID39437789
PMCPMC11663113

What OpenQuestion holds

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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.