Evidence map›Paper›PMID 30562414›Full record

ArticleChemMedChem2019

Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins: Exploration of the N3 and N9 Positions and Interaction with Multidrug-Resistance Proteins.

Ramesh Dasari, Andrzej Błauż, Derek C Medellin, Roaa M Kassim, Carlos Viera, Maximo Santarosa, Alet E van der Westhuyzen, Willem A L van Otterlo, Taryn Olivas, Tugba Yildiz and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2019. 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
0.2field-weighted citation impact, top 49% 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, 6 citations in OpenAlex.

  1. 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

17 authors at 5 institutions in 3 countries.

Ramesh DasariDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.
Andrzej BłaużCytometry Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, ul. Pomorska 141/143, 90-236, Łódź, Poland.
Derek C MedellinDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.
Roaa M KassimDepartment of Biology, New Mexico State University, Las Cruces, NM, 88003, USA.
Carlos VieraDepartments of Chemistry and Biology, New Mexico Tech, Socorro, NM, 87801, USA.
Maximo SantarosaDepartments of Chemistry and Biology, New Mexico Tech, Socorro, NM, 87801, USA.
Alet E van der WesthuyzenDepartment of Chemistry and Polymer Science, University of Stellenbosch, 7602, Stellenbosch, South Africa.
Willem A L van OtterloDepartment of Chemistry and Polymer Science, University of Stellenbosch, 7602, Stellenbosch, South Africa.
Taryn OlivasDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.
Tugba YildizMaterials Science and Engineering Program, Texas State University, San Marcos, TX, 78666, USA.
Tania BetancourtDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.ORCID 0000-0002-2460-6133
Charles B ShusterDepartment of Biology, New Mexico State University, Las Cruces, NM, 88003, USA.
Snezna RogeljDepartments of Chemistry and Biology, New Mexico Tech, Socorro, NM, 87801, USA.
Błażej RychlikCytometry Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, ul. Pomorska 141/143, 90-236, Łódź, Poland.
Todd HudnallDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.
Liliya V FrolovaDepartments of Chemistry and Biology, New Mexico Tech, Socorro, NM, 87801, USA.
Alexander KornienkoDepartment of Chemistry and Biochemistry, Texas State University, San Marcos, TX, 78666, USA.ORCID 0000-0003-2041-7367
Texas State University · USNew Mexico Institute of Mining and Technology · USNew Mexico State University · USStellenbosch University · ZAUniversity of Łódź · PL

Funding

NM-INBRE Sequencing and Bioinformatics CoreP20GM103451 · NIGMS · NEW MEXICO STATE UNIVERSITY LAS CRUCES · PI Charlotte C. Gard · 2012 to 2026
$61.2M
Mode of Action of the Amaryllidaceae Alkaloid Lycorine-Promising Anticancer AgentR15CA186046 · NCI · TEXAS STATE UNIVERSITY · PI KORNIENKO, ALEXANDER · 2014 to 2014
$476k
NCI NIH HHS R15 CA186046NIGMS NIH HHS P20 GM103451
6 · The paper itself

Abstract

Our laboratories have been investigating synthetic analogues of marine alkaloid rigidins that possess promising anticancer activities. These analogues, based on the 7-deazahypoxanthine skeleton, are available in one- or two-step synthetic sequences and exert cytotoxicity by disrupting microtubule dynamics in cancer cells. In the present work we extended the available structure-activity relationship (SAR) data to N3- and N9-substituted derivatives. Although N3 substitution results in loss of activity, the N9-substituted compounds retain nanomolar antiproliferative activities and the anti-tubulin mode of action of the original unsubstituted compounds. Furthermore, our results also demonstrate that multidrug-resistance (MDR) proteins do not confer resistance to both N9-unsubstituted and -substituted compounds. It was found that sublines overexpressing ABCG2, ABCC1, and ABCB1 proteins are as responsive to the rigidin analogues as their parental cell lines. Thus, the study reported herein provides further impetus to investigate the rigidin-inspired 7-deazahypoxanthines as promising anticancer agents.

Indexed as

AlkaloidsAnimalsAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BCell ProliferationDogsDose-Response Relationship, DrugDrug Screening Assays, AntitumorHeLa CellsHumansHypoxanthineMadin Darby Canine Kidney CellsMCF-7 CellsMicrotubulesMolecular StructurePyrimidinesAlkaloidsAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BHypoxanthinePyrimidinesPyrrolesrigidin Arigidin Brigidin Crigidin D7-deazapurinesalkaloidsantitumor agentsdrug discoverypyrrolo[2,3-d]pyrimidines

Identifiers

PMID30562414
PMCPMC6476547
OpenAlexW2904295959

What OpenQuestion holds

Textmetadata
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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.