Evidence map›Paper›PMID 35697660›Full record

ArticleChemistry (Weinheim an der Bergstrasse, Germany)2022

Cephem-Pyrazinoic Acid Conjugates: Circumventing Resistance in Mycobacterium tuberculosis.

Malcolm S Cole, Michael D Howe, Joseph A Buonomo, Sachin Sharma, Elise A Lamont, Scott I Brody, Neeraj K Mishra, Yusuke Minato, Joshua M Thiede, Anthony D Baughn and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2022. 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
0.4field-weighted citation impact, top 40% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. 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

11 authors at 1 institution in 3 countries.

Malcolm S ColeDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, Minneapolis, Minnesota 55455, USA.
Michael D HoweDepartment of Microbiology, Immunology, University of Minnesota Medical School, 689 23rd Ave SE, Minneapolis, Minnesota 55455, USA.
Joseph A BuonomoDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, Minneapolis, Minnesota 55455, USA.
Sachin SharmaDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, Minneapolis, Minnesota 55455, USA.
Elise A LamontDepartment of Microbiology, Immunology, University of Minnesota Medical School, 689 23rd Ave SE, Minneapolis, Minnesota 55455, USA.
Scott I BrodyDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, Minneapolis, Minnesota 55455, USA.
Neeraj K MishraDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, Minneapolis, Minnesota 55455, USA.
Yusuke MinatoDepartment of Microbiology, Immunology, University of Minnesota Medical School, 689 23rd Ave SE, Minneapolis, Minnesota 55455, USA.
Joshua M ThiedeDepartment of Microbiology, Immunology, University of Minnesota Medical School, 689 23rd Ave SE, Minneapolis, Minnesota 55455, USA.
Anthony D BaughnDepartment of Microbiology, Immunology, University of Minnesota Medical School, 689 23rd Ave SE, Minneapolis, Minnesota 55455, USA.
Courtney C AldrichDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, Minneapolis, Minnesota 55455, USA.ORCID http://orcid.org/0000-0001-9261-594X
University of Minnesota · US

Funding

Chemistry-Biology Interface Training GrantT32GM008700 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI DISTEFANO, MARK D · 1999 to 2018
$4.0M
Overcoming Pyrazinamide Resistance with Pyrazinoate-Cephalosporin ConjugatesR21AI144501 · NIAID · UNIVERSITY OF MINNESOTA · PI ALDRICH, COURTNEY C, BAUGHN, ANTHONY D · 2020 to 2021
$421k
NIAID NIH HHS R21 AI144501NIGMS NIH HHS T32 GM008700NIGMS NIH HHS T32GM008700
6 · The paper itself

Abstract

Tuberculosis (TB) is a leading source of infectious disease mortality globally. Antibiotic-resistant strains comprise an estimated 10 % of new TB cases and present an urgent need for novel therapeutics. β-lactam antibiotics have traditionally been ineffective against M. tuberculosis (Mtb), the causative agent of TB, due to the organism's inherent expression of β-lactamases that destroy the electrophilic β-lactam warhead. We have developed novel β-lactam conjugates, which exploit this inherent β-lactamase activity to achieve selective release of pyrazinoic acid (POA), the active form of a first-line TB drug. These conjugates are selectively active against M. tuberculosis and related mycobacteria, and activity is retained or even potentiated in multiple resistant strains and models. Preliminary mechanistic investigations suggest that both the POA "warhead" as well as the β-lactam "promoiety" contribute to the observed activity, demonstrating a codrug strategy with important implications for future TB therapy.

Indexed as

Mycobacterium tuberculosisTuberculosisAntitubercular Agentsbeta-LactamsHumansMicrobial Sensitivity TestsPyrazinamideAntitubercular Agentsbeta-LactamsPyrazinamidepyrazinoic acidbeta-lactamasecephalosporinmycobacterium tuberculosisnew antibioticspyrazinamide

Identifiers

PMID35697660
PMCPMC9474573
OpenAlexW4282831176

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.