| Literature DB >> 33603968 |
Simon Leiris1, David T Davies1, Nicolas Sprynski1, Jérôme Castandet1, Lilha Beyria1, Michael S Bodnarchuk2, Jonathan M Sutton2, Toby M G Mullins2, Mark W Jones2, Andrew K Forrest2, T David Pallin2, Paduri Karunakar3, Sathish Kumar Martha3, Battu Parusharamulu3, Ramesh Ramula3, Venkatesh Kotha3, Narender Pottabathini3, Srinivasu Pothukanuri3, Marc Lemonnier1, Martin Everett1.
Abstract
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).Entities:
Year: 2021 PMID： 33603968 PMCID： PMC7883467 DOI： 10.1021/acsmedchemlett.0c00554
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345