Evidence map›Paper›PMID 24644272›Full record

ArticleChemMedChem2014

Synthetic and biological studies of tubulin targeting c2-substituted 7-deazahypoxanthines derived from marine alkaloid rigidins.

Robert Scott, Menuka Karki, Mary R Reisenauer, Roberta Rodrigues, Ramesh Dasari, W Ross Smith, Stephen C Pelly, Willem A L van Otterlo, Charles B Shuster, Snezna Rogelj and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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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

13 authors.

Robert Scott *Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.
Menuka Karki *Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA.
Mary R ReisenauerDepartments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
Roberta RodriguesDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.
Ramesh DasariDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.
W Ross SmithDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.
Stephen C PellyDepartment of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Private Bag X1, Matieland, 7602, South Africa.
Willem A L van OtterloDepartment of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, Private Bag X1, Matieland, 7602, South Africa.
Charles B ShusterDepartment of Biology, New Mexico State University, Las Cruces, NM 88003, USA.
Snezna RogeljDepartments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
Igor V MagedovDepartments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
Liliya V FrolovaDepartments of Chemistry and Biology, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA.
Alexander KornienkoDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.

Funding

NM-INBRE Sequencing and Bioinformatics CoreP20GM103451 · NIGMS · NEW MEXICO STATE UNIVERSITY LAS CRUCES · PI Charlotte C. Gard · 2012 to 2026
$61.2M
NIGMS NIH HHS P20 GM103451NIGMS NIH HHS P20GM103451
6 · The paper itself

Abstract

C2-aryl- and C2-alkyl-7-deazahypoxanthines as analogues of marine alkaloid rigidins were prepared utilizing novel synthetic methods developed for the construction of the pyrrolo[2,3-d]pyrimidine ring system. The new compounds exhibited sub-micromolar to nanomolar antiproliferative potencies against a panel of cell lines including in vitro models for drug-resistant tumors, such as glioblastoma, melanoma and non-small-cell lung cancer. A selected representative C2-methyl-7-deazahypoxanthine was found to inhibit microtubule dynamics in cancer cells, lending evidence for tubulin targeting as a mode of action for these compounds in cancer cells. The results of the docking studies utilizing the colchicine site on β-tubulin were consistent with the observed structure-activity relationship data, including an important finding that derivatization at C2 with linear alkyl groups leads to the retention of activity, thus permitting the attachment of a biotin-containing linker for the subsequent proteomics assays. Because many microtubule-targeting compounds are successfully used to fight cancer in the clinic, the reported antitubulin rigidin analogues have significant potential as new anticancer agents.

Indexed as

AlkaloidsBinding SitesCell Line, TumorCell SurvivalHeLa CellsHumansHypoxanthinesMCF-7 CellsMicroscopy, VideoMolecular Docking SimulationProtein Structure, TertiaryPyrimidinesPyrrolesStructure-Activity RelationshipTubulinTubulin ModulatorsAlkaloidsHypoxanthinesPyrimidinesPyrrolesPyrrolo(2,3-d)pyrimidineTubulinTubulin Modulators7-deazapurinesalkaloidsdrug discoveryprivileged structurespyrrolo[2,3-d]pyrimidines

Identifiers

PMID24644272
PMCPMC4945961

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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.