Virtual Screening Approach to Identifying a Novel and Tractable Series of Pseudomonas aeruginosa Elastase Inhibitors.
In: ACS medicinal chemistry letters, Jg. 12 (2021-01-15), Heft 2, S. 217-227
Online
academicJournal
Zugriff:
Novel therapies are required to treat chronic bacterial infections in cystic fibrosis (CF) sufferers. The most common pathogen responsible for these infections is Pseudomonas aeruginosa , which persists within the lungs of CF sufferers despite intensive antibiotic treatment. P. aeruginosa elastase (also known as LasB or pseudolysin) is a key virulence determinant that contributes to the pathogenesis and persistence of P. aeruginosa infections in CF patients. The crucial role of LasB in pseudomonal virulence makes it a good target for the development of an adjuvant drug for CF treatment. Herein we discuss the discovery of a new series of LasB inhibitors by virtual screening and computer assisted drug design (CADD) and their optimization leading to compounds 29 and 39 ( K i = 0.16 μM and 0.12 μM, respectively).
Competing Interests: The authors declare no competing financial interest.
(© 2021 American Chemical Society.)
| Titel: |
Virtual Screening Approach to Identifying a Novel and Tractable Series of Pseudomonas aeruginosa Elastase Inhibitors.
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| Autor/in / Beteiligte Person: | Leiris, S ; Davies, DT ; Sprynski, N ; Castandet, J ; Beyria, L ; Bodnarchuk, MS ; Sutton, JM ; Mullins, TMG ; Jones, MW ; Forrest, AK ; Pallin, TD ; Karunakar, P ; Martha, SK ; Parusharamulu, B ; Ramula, R ; Kotha, V ; Pottabathini, N ; Pothukanuri, S ; Lemonnier, M ; Everett, M |
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| Zeitschrift: | ACS medicinal chemistry letters, Jg. 12 (2021-01-15), Heft 2, S. 217-227 |
| Veröffentlichung: | Washington, D.C. : American Chemical Society, 2021 |
| Medientyp: | academicJournal |
| ISSN: | 1948-5875 (print) |
| DOI: | 10.1021/acsmedchemlett.0c00554 |
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