Evidence map›Paper›PMID 35660840›Full record

ArticleBioorganic chemistry2022

Cytotoxicity of phenylpironetin analogs and the metabolic fate of pironetin and phenylpironetin.

Md Abdullah Al Noman, David S Huang, Sara K Coulup, Shameem Sultana Syeda, Henry, L Wong, Gunda I Georg

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic chemistry, 2022. 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
–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

1 citing paper in PubMed.

  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

7 authors.

Md Abdullah Al NomanDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, MN 55414, United States.
David S HuangDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, MN 55414, United States.
Sara K CoulupDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, MN 55414, United States.
Shameem Sultana SyedaDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, MN 55414, United States.
HenryDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, MN 55414, United States.
L WongDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, MN 55414, United States.
Gunda I GeorgDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, MN 55414, United States. Electronic address: georg@umn.edu.

Funding

Chemistry-Biology Interface Training GrantT32GM008700 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI DISTEFANO, MARK D · 1999 to 2018
$4.0M
Training the Next Generation of Chemical BiologistsT32GM132029 · NIGMS · UNIVERSITY OF MINNESOTA · PI Erin Elizabeth Carlson, William Charles Krause Pomerantz · 2019 to 2026
$2.7M
Design and synthesis of stabilized pironetin analogs for the treatment of resistant ovarian cancersF31CA203039 · NCI · UNIVERSITY OF MINNESOTA · PI COULUP, SARA K · 2016 to 2019
$93k
NCI NIH HHS F31 CA203039NIGMS NIH HHS T32 GM008700NIGMS NIH HHS T32 GM132029
6 · The paper itself

Abstract

To improve pironetin's metabolic stability we prepared four analogs by replacing its C12-14 segment with an aryl group. The antiproliferative activity of phenyl analog 4 was reduced two-fold and dihydroxy-4-fluorophenyl analog 5 was slightly more effective against OVCAR5 and A2780 ovarian cancer cell lines compared with the parent compound pironetin (1). The activity of 4-fluorophenyl analog 6 was reduced 3-fold in both cell lines. The activity of 7-O-methyl analog 7 was reduced 36-fold in OVCAR5 cells and 47-fold and A2780 cells, compared with pironetin. Phenylpironetin (4) was rapidly metabolized by mouse and human liver microsomes. We identified 17 human metabolites for phenyl analog 4 and 14 human metabolites for pironetin. Metabolism occurred at the C12-13 moiety, the α,β-unsaturated lactone and the side chains of the molecules (C6-C11 segments). The significant extent of oxidative metabolism suggests that it may not be possible to attain a metabolically stable pironetin analog by structural modifications of the parent compound.

Indexed as

Ovarian NeoplasmsAnimalsCell Line, TumorFemaleHumansLactonesMicePyronesLactonespironetinPyronesAnalogsAntiproliferationMetabolismPironetinTotal synthesis

Identifiers

PMID35660840
PMCPMC11557558

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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.