Antibacterial activity of noscapine analogs.
Bioorg Med Chem Lett
; 43: 128055, 2021 07 01.
Article
in En
| MEDLINE
| ID: mdl-33892103
ABSTRACT
The antibacterial properties of close noscapine analogs have not been previously reported. We used our pDualrep2 double-reporter High Throughput Screening (HTS) platform to identify a series of noscapine derivatives with promising antibacterial activity. The platform is based on RPF (SOS-response/DNA damage) and Katushka2S (inhibition of translation) proteins and simultaneously provides information on antibacterial activity and the mechanism of action of small-molecule compounds against E. coli. The most potent compound exhibited an MIC of 13.5 µM(6.25 µg/ml) and a relatively low cytotoxicity against HEK293 cells (CC50 = 71 µM, selectivity index ~5.5). Some compounds from this series induced average Katushka2S reporter signals, indicating inhibition of translation machinery in the bacteria; however, these compounds did not attenuate translation in vitro in a luciferase-based translation assay. The most effective compounds did not significantly arrest the mitotic cycle in HEK293 cells, in contrast to the parent compound in a flow cytometry assay. Several molecules showed activity against clinically relevant gram-negative and gram-positive bacterial strains. Compounds from the discovered series can be reasonably regarded as good templates for further development and evaluation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gram-Negative Bacteria
/
Gram-Positive Bacteria
/
Anti-Bacterial Agents
/
Noscapine
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2021
Document type:
Article