Identification of Novel Mycobacterial Inhibitors Against Mycobacterial Protein Kinase G

Kanehiro, Yuichi and Tomioka, Haruaki and Pieters, Jean and Tatano, Yutaka and Kim, Hyoji and Iizasa, Hisashi and Yoshiyama, Hironori. (2018) Identification of Novel Mycobacterial Inhibitors Against Mycobacterial Protein Kinase G. Frontiers in Microbiology, 9. p. 1517.

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Protein kinase G (PknG) is a eukaryotic-like serine/threonine kinase that is expressed by; Mycobacterium tuberculosis; and promotes survival of mycobacteria in host macrophages by suppressing phagosome-lysosome fusion. Thus, compounds showing inhibitory activity against PknG are promising anti-mycobacterial agents. We therefore aimed to develop anti-mycobacterial agents by identifying new PknG inhibitors. A luciferase-based PknG kinase assay was used to screen potential inhibitors of PknG. We found that four compounds, namely AZD7762, R406, R406-free base, and CYC116, inhibited PknG activities. AZD7762, R406, and R406-free base promoted transfer of mycobacteria to lysosomes. These compounds also inhibited survival of; M. bovis; Bacillus Calmette-Guérin (BCG) inside human macrophages. Furthermore, R406 and R406-free base showed bactericidal activity against BCG in infected human macrophages without cytotoxicity. The PknG inhibitors identified in this study by the luciferase-based PknG kinase assay may be promising leads for the development of anti-mycobacterial agents.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Biochemistry (Pieters)
UniBasel Contributors:Pieters, Jean
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Frontiers Media
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:12 Sep 2018 09:50
Deposited On:12 Sep 2018 09:50

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