bei Google ScholarTitelangaben
Guzman, Juan D. ; Pesnot, Thomas ; Barrera, Diana Astrid ; Davies, Heledd M. ; McMahon, Eleanor ; Evangelopoulos, Dimitrios ; Mortazavi, Parisa N. ; Munshi, Tulika ; Maitra, Arundhati ; Lamming, Eleanor D. ; Angell, Richard ; Gershater, Markus C. ; Redmond, Joanna M. ; Needham, Deborah ; Ward, John M. ; Cuca, Luis E. ; Hailes, Helen C. ; Bhakta, Sanjib:
Tetrahydroisoquinolines affect the whole-cell phenotype of Mycobacterium tuberculosis by inhibiting the ATP-dependent MurE ligase.
In: Journal of Antimicrobial Chemotherapy.
Bd. 70
(2015)
Heft 6
.
- S. 1691-1703.
ISSN 0305-7453
DOI: https://doi.org/10.1093/jac/dkv010
Abstract
Objectives
(S)-Leucoxine, isolated from the Colombian Lauraceae tree Rhodostemonodaphne crenaticupula Madriñan, was found to inhibit the growth of Mycobacterium tuberculosis H37Rv. A biomimetic approach for the chemical synthesis of a wide array of 1-substituted tetrahydroisoquinolines was undertaken with the aim of elucidating a common pharmacophore for these compounds with novel mode(s) of anti-TB action.
Methods
Biomimetic Pictet–Spengler or Bischler–Napieralski synthetic routes were employed followed by an evaluation of the biological activity of the synthesized compounds.
Results
In this work, the synthesized tetrahydroisoquinolines were found to inhibit the growth of M. tuberculosis H37Rv and affect its whole-cell phenotype as well as the activity of the ATP-dependent MurE ligase, a key enzyme involved in the early stage of cell wall peptidoglycan biosynthesis.
Conclusions
As the correlation between the MIC and the half-inhibitory enzymatic concentration was not particularly strong, there is a credible possibility that these compounds have pleiotropic mechanism(s) of action in M. tuberculosis.
Weitere Angaben
| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Keywords: | tuberculosis; TB; Mycobacterium tuberculosis; drug resistance; cell wall peptidoglycan; aporphine alkaloids; SPOTi |
| Institutionen der Universität: | Fakultäten > Fakultät für Lebenswissenschaften: Lebensmittel, Ernährung und Gesundheit > Lehrstuhl Bioanalytik und Lebensmittelanalytik |
| Titel an der UBT entstanden: | Nein |
| Themengebiete aus DDC: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie |
| Eingestellt am: | 30 Apr 2025 09:53 |
| Letzte Änderung: | 30 Apr 2025 09:53 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/93410 |