Evidence map›Paper›PMID 26071634›Full record

ArticleBioorganic & medicinal chemistry letters2015

Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin.

Tao Liu, Ming Ma, Hui-Ming Ge, Chunying Yang, John Cleveland, Ben Shen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Recent synthesis of thietanes.Beilstein journal of organic chemistry · 2020
    Review
  2. Article
  3. Discovery of the leinamycin family of natural products by mining actinobacterial genomes.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  4. Article
  5. 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

6 authors at 2 institutions in 1 country.

Tao LiuDivision of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53705, USA.
Ming MaDepartment of Chemistry, The Scripps Research Institute, 130 Scripps Way, #3A1, Jupiter, FL 33458, USA.
Hui-Ming GeDepartment of Chemistry, The Scripps Research Institute, 130 Scripps Way, #3A1, Jupiter, FL 33458, USA.
Chunying YangDepartment of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
John ClevelandDepartment of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Ben ShenDivision of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, #3A1, Jupiter, FL 33458, USA; Department of Molecular Therapeutics, The Scripps Research Institute, 130 Scripps Way, #3A1, Jupiter, FL 33458, USA; Natural Products Library Initiative, The Scripps Research Institute, 130 Scripps Way, #3A1, Jupiter, FL 33458, USA. Electronic address: shenb@scripps.edu.
Scripps Research Institute · USUniversity of Wisconsin–Madison · US

Funding

AT-less Type I Polyketide SynthasesR01CA106150 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI SHEN, BEN · 2004 to 2015
$3.3M
NCI NIH HHS CA106150NCI NIH HHS R01 CA106150
6 · The paper itself

Abstract

Leinamycin (LNM, 1) is a novel antitumor antibiotic produced by Streptomyces atroolivaceus S-140 and features an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety of LNM is essential for its antitumor activity via an episulfonium ion-mediated DNA alkylation upon reductive activation in the presence of cellular thiols. We recently isolated leinamycin E1 (LNM E1, 2) from an engineered strain S. atroolivaceus SB3033, which lacks the 1,3-dioxo-1,2-dithiolane moiety. Here we report the chemical synthesis of 8,4'-dideshydroxy-LNM (5) from 2 and determination of the cytotoxicity of 5 against selected cancer cell lines in comparison with 1; 5 exhibits comparable activity as 1 with the EC50 values between 8.21 and 275 nM. This work reveals new insight into the structure-activity relationship of LNM and highlights the synergy between metabolic pathway engineering and medicinal chemistry for natural product drug discovery.

Indexed as

Antibiotics, AntineoplasticBiological ProductsCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansLactamsMolecular ConformationStreptomycesStructure-Activity RelationshipThiazoles8,4'-dideshydroxy-leinamycinAntibiotics, AntineoplasticBiological ProductsLactamsThiazolesAntitumor antibioticDNA alkylationLeinamycinMetabolic pathway engineeringStructure–activity relationship

Identifiers

PMID26071634
PMCPMC4607584
OpenAlexW801871431

What OpenQuestion holds

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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.