Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/116641
Title: Broad-spectrum in vitro activity of Nα-aroyl-N-aryl-phenylalanine amides against non-tuberculous mycobacteria and comparative analysis of RNA polymerases
Author(s): Lang, Markus
Ganapathy, Uday S.
Abdelaziz, RanaLook up in the Integrated Authority File of the German National Library
Dick, ThomasLook up in the Integrated Authority File of the German National Library
Richter, AdrianLook up in the Integrated Authority File of the German National Library
Issue Date: 2024
Type: Article
Language: English
Abstract: This study investigates the in vitro activity of Nα-aroyl-N-aryl-phenylalanine amides (AAPs), previously identified as antimycobacterial RNA polymerase (RNAP) inhibitors, against a panel of 25 non-tuberculous mycobacteria (NTM). The compounds, including the hit compound MMV688845, were selected based on their structural diversity and previously described activity against mycobacteria. Bacterial strains, including the M. abscessus complex, M. avium complex, and other clinically relevant NTM, were cultured and subjected to growth inhibition assays. The results demonstrate significant activity against the most common NTM pathogens from the M. abscessus and M. avium complexes. Variations in activity were observed against other NTM species, with for instance M. ulcerans displaying high susceptibility and M. xenopi and M. simiae resistance to AAPs. Comparative analysis of RNAP β and β′ subunits across mycobacterial species revealed strain-specific polymorphisms, providing insights into differential compound susceptibility. While conservation of target structures was observed, differences in compound activity suggested influences beyond drug–target interactions. This study highlights the potential of AAPs as effective antimycobacterial agents and emphasizes the complex interplay between compound structure, bacterial genetics, and in vitro activity.
URI: https://opendata.uni-halle.de//handle/1981185920/118597
http://dx.doi.org/10.25673/116641
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Journal Title: Antibiotics
Publisher: MDPI
Publisher Place: Basel
Volume: 13
Issue: 5
Original Publication: 10.3390/antibiotics13050404
Page Start: 1
Page End: 14
Appears in Collections:Open Access Publikationen der MLU

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