Evidence map›Paper›PMID 37755087›Full record

ArticleMarine drugs2023

An Investigation of Structure-Activity Relationships and Cell Death Mechanisms of the Marine Alkaloids Discorhabdins in Merkel Cell Carcinoma Cells.

Maria Orfanoudaki, Emily A Smith, Natasha T Hill, Khalid A Garman, Isaac Brownell, Brent R Copp, Tanja Grkovic, Curtis J Henrich

Open access · goldAbstract read
In one paragraph

Article in Marine drugs, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 13% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. New Discorhabdin D Analogues fromJournal of natural products · 2024
    Article
  5. Chemoreactive 2,5-Diketopiperazines from aJournal of natural products · 2024
    Article
  6. 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

8 authors at 3 institutions in 2 countries.

Maria OrfanoudakiMolecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.ORCID 0000-0002-9409-7645
Emily A SmithMolecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.ORCID 0000-0001-8869-2336
Natasha T HillDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20891, USA.ORCID 0000-0001-9043-4643
Khalid A GarmanDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20891, USA.
Isaac BrownellDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20891, USA.ORCID 0000-0002-0090-9914
Brent R CoppSchool of Chemical Sciences, University of Auckland, Auckland 1142, New Zealand.ORCID 0000-0001-5492-5269
Tanja GrkovicMolecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Curtis J HenrichMolecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Target (United States) · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · USUniversity of Auckland · NZ

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
NCI NIH HHS 75N91019D00024
6 · The paper itself

Abstract

A library of naturally occurring and semi-synthetic discorhabdins was assessed for their effects on Merkel cell carcinoma (MCC) cell viability. The set included five new natural products and semi-synthetic compounds whose structures were elucidated with NMR, HRMS, and ECD techniques. Several discorhabdins averaged sub-micromolar potency against the MCC cell lines tested and most of the active compounds showed selectivity towards virus-positive MCC cell lines. An investigation of structure-activity relationships resulted in an expanded understanding of the crucial structural features of the discorhabdin scaffold. Mechanistic cell death assays suggested that discorhabdins, unlike many other MCC-active small molecules, do not induce apoptosis, as shown by the lack of caspase activation, annexin V staining, and response to caspase inhibition. Similarly, discorhabdin treatment failed to increase MCC intracellular calcium and ROS levels. In contrast, the rapid loss of cellular reducing potential and mitochondrial membrane potential suggested that discorhabdins induce mitochondrial dysfunction leading to non-apoptotic cell death.

Indexed as

AlkaloidsCarcinoma, Merkel CellSkin NeoplasmsCaspasesCell DeathHumansStructure-Activity RelationshipAlkaloidsCaspasesdiscorhabdinmechanism of actionMerkel cell carcinomastructure–activity relationship

Identifiers

PMID37755087
PMCPMC10532587
OpenAlexW4386254866

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.