Evidence map›Paper›PMID 18156292›Full record

ArticleEukaryotic cell2008

Role of heme in the antifungal activity of the azaoxoaporphine alkaloid sampangine.

Ameeta K Agarwal, Tao Xu, Melissa R Jacob, Qin Feng, Michael C Lorenz, Larry A Walker, Alice M Clark

Open access · diamondAbstract read
In one paragraph

Article in Eukaryotic cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

21 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. The Interkingdom Interaction withJournal of microbiology and biotechnology · 2023
    Article
  3. Review
  4. Review
  5. Biological Activity of Naturally Derived Naphthyridines.Molecules (Basel, Switzerland) · 2021
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. New Horizons in Antifungal Therapy.Journal of fungi (Basel, Switzerland) · 2016
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
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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

7 authors at 2 institutions in 1 country.

Ameeta K AgarwalNational Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA. aagarwal@olemiss.edu
Tao Xu
Melissa R Jacob
Qin Feng
Michael C Lorenz
Larry A Walker
Alice M Clark
The University of Texas Health Science Center at Houston · USUniversity of Mississippi · US

Funding

NEW DRUGS FOR OPPORTUNISTIC INFECTIOUS DISEASESR01AI027094 · NIAID · UNIVERSITY OF MISSISSIPPI · PI CLARK, ALICE M. · 1989 to 2013
$4.4M
Roles of acetate metabolism in the virulence of Candida albicansR01AI075091 · NIAID · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LORENZ, MICHAEL C · 2007 to 2017
$4.0M
NIAID NIH HHS R01 AI027094NIAID NIH HHS R01 AI075091NIAID NIH HHS R01 AI27094
6 · The paper itself

Abstract

Sampangine, a plant-derived alkaloid found in the Annonaceae family, exhibits strong inhibitory activity against the opportunistic fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. In the present study, transcriptional profiling experiments coupled with analyses of mutants were performed in an effort to elucidate its mechanism of action. Using Saccharomyces cerevisiae as a model organism, we show that sampangine produces a transcriptional response indicative of hypoxia, altering the expression of genes known to respond to low-oxygen conditions. Several additional lines of evidence obtained suggest that these responses could involve effects on heme. First, the hem1Delta mutant lacking the first enzyme in the heme biosynthetic pathway showed increased sensitivity to sampangine, and exogenously supplied hemin partially rescued the inhibitory activity of sampangine in wild-type cells. In addition, heterozygous mutants with deletions in genes involved in five out of eight steps in the heme biosynthetic pathway showed increased susceptibility to sampangine. Furthermore, spectral analyses of pyridine extracts indicated significant accumulation of free porphyrins in sampangine-treated cells. Transcriptional profiling experiments were also performed with C. albicans to investigate the response of a pathogenic fungal species to sampangine. Taking into account the known differences in the physiological responses of C. albicans and S. cerevisiae to low oxygen, significant correlations were observed between the two transcription profiles, suggestive of heme-related defects. Our results indicate that the antifungal activity of the plant alkaloid sampangine is due, at least in part, to perturbations in the biosynthesis or metabolism of heme.

Indexed as

Cell HypoxiaAlkaloidsAntifungal AgentsCandida albicansGene Expression ProfilingGene Expression Regulation, FungalHemeHeterocyclic Compounds, 4 or More RingsNaphthyridinesOligonucleotide Array Sequence AnalysisOxygenPyridinesRNA, FungalSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription, GeneticAlkaloidsAntifungal AgentsHemeHeterocyclic Compounds, 4 or More RingsNaphthyridinesOxygenpyridinePyridinesRNA, FungalSaccharomyces cerevisiae Proteinssampangine

Identifiers

PMID18156292
PMCPMC2238161
OpenAlexW2131909808

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.