Novel chemical entities inhibiting Mycobacterium tuberculosis growth identified by phenotypic high-throughput screening.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
received:
01
03
2022
accepted:
25
08
2022
entrez:
1
9
2022
pubmed:
2
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
We performed a high-throughput phenotypic whole cell screen of Mycobacterium tuberculosis against a diverse chemical library of approximately 100,000 compounds from the AbbVie corporate collection and identified 24 chemotypes with anti-tubercular activity. We selected two series for further exploration and conducted structure-activity relationship studies with new analogs for the 4-phenyl piperidines (4PP) and phenylcyclobutane carboxamides (PCB). Strains with mutations in MmpL3 demonstrated resistance to both compound series. We isolated resistant mutants for the two series and found mutations in MmpL3. These data suggest that MmpL3 is the target, or mechanism of resistance for both series.
Identifiants
pubmed: 36050506
doi: 10.1038/s41598-022-19192-7
pii: 10.1038/s41598-022-19192-7
pmc: PMC9435431
doi:
Substances chimiques
Antitubercular Agents
0
Bacterial Proteins
0
Membrane Transport Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14879Subventions
Organisme : Bill & Melinda Gates Foundation
ID : OPP1024038
Pays : United States
Informations de copyright
© 2022. The Author(s).
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