Antibacterial activity of noscapine analogs
| Autor: | A. A. Vladimirova, Ayrat R. Mavzyutov, Yan A. Ivanenkov, Kseniya Yu. Filyaeva, Victor G Kartsev, Valeriya I. Marina, Victor A Terentiev, Renat S. Yamidanov, Olga A. Dontsova, Andrey Baymiev, Julia V. Vakhitova, R.T. Matniyazov, Ilya A. Osterman, Dmitry S. Bezrukov, Alexey Kh. Baymiev, L. F. Zainullina, Zulfia R. Zileeva |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Noscapine
Cell Survival DNA damage High-throughput screening Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Gram-Positive Bacteria 01 natural sciences Biochemistry Structure-Activity Relationship Gram-Negative Bacteria Drug Discovery medicine Humans Luciferase Cytotoxicity Molecular Biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry In vitro Anti-Bacterial Agents 0104 chemical sciences 010404 medicinal & biomolecular chemistry HEK293 Cells Mechanism of action Molecular Medicine medicine.symptom Antibacterial activity medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 43:128055 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2021.128055 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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