Evidence map›Paper›PMID 25677656›Full record

ArticleBioorganic & medicinal chemistry letters2015

A novel molecule with notable activity against multi-drug resistant tuberculosis.

Vasu Nair, Maurice O Okello, Naveen K Mangu, Byung I Seo, Machhindra G Gund

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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Molecule Property Analyses of Active Compounds forJournal of medicinal chemistry · 2020
    Review
  4. Review
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

5 authors.

Vasu NairUGA Center for Drug Discovery and the College of Pharmacy, University of Georgia, R.C. Wilson Pharmacy, Room 320A, Athens, GA 30602, USA. Electronic address: vnair@uga.edu.
Maurice O OkelloUGA Center for Drug Discovery and the College of Pharmacy, University of Georgia, R.C. Wilson Pharmacy, Room 320A, Athens, GA 30602, USA.
Naveen K ManguUGA Center for Drug Discovery and the College of Pharmacy, University of Georgia, R.C. Wilson Pharmacy, Room 320A, Athens, GA 30602, USA.
Byung I SeoUGA Center for Drug Discovery and the College of Pharmacy, University of Georgia, R.C. Wilson Pharmacy, Room 320A, Athens, GA 30602, USA.
Machhindra G GundUGA Center for Drug Discovery and the College of Pharmacy, University of Georgia, R.C. Wilson Pharmacy, Room 320A, Athens, GA 30602, USA.

Funding

VIRAL REPLICATION INHIBITORS TARGETED AT HIV INTEGRASER01AI043181 · NIAID · UNIVERSITY OF IOWA · PI NAIR, VASU · 1998 to 2004
$1.2M
NIAID NIH HHS R01 AI043181NIAID NIH HHS R01 AI 43181
6 · The paper itself

Abstract

Multi-drug resistant tuberculosis (MDR-TB) is emerging as a serious global health problem, which has been elevated through co-infection involving HIV and MDR-Mtb. The discovery of new compounds with anti-MDR TB efficacy and favorable metabolism profiles is an important scientific challenge. Using computational biology and ligand docking data, we have conceived a multifunctional molecule, 2, as a potential anti-MDR TB agent. This compound was produced through a multi-step synthesis. It exhibited significant in vitro activity against MDR-TB (MIC 1.56μg/mL) and its half-life (t1/2) in human liver microsomes was 14.4h. The metabolic profiles of compound 2 with respect to human cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) isozymes were favorable. Compound 2 also had relatively low in vitro cytotoxicity in uninfected macrophages. It displayed synergistic behavior against MDR-TB in combination with PA-824. Interestingly, compound 2 also displayed in vitro anti-HIV activity.

Indexed as

Antitubercular AgentsCytochrome P-450 Enzyme SystemDrug DesignDrug SynergismGlucuronosyltransferaseHalf-LifeHumansMicrobial Sensitivity TestsMicrosomes, LiverMycobacterium tuberculosisNitroimidazolesPiperazinesPyridonesTuberculosis, Multidrug-Resistant1-(4-(4-(1H-pyrrol-1-yl)phenyl)piperazin-1-yl)-4-(5-(3,5-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-hydroxybut-2-ene-1,4-dioneAntitubercular AgentsCytochrome P-450 Enzyme SystemGlucuronosyltransferaseNitroimidazolesPiperazinespretomanidPyridonesAnti-MDR TBCYP and UGT profilesDrug discoverySynergism

Identifiers

PMID25677656
PMCPMC4348211

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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.