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Anti-Infective Agents, том 18, издание 2, номера страниц: 121-127

Tetrahydrocarbazoles as novel class of DNA biosynthesis inhibitors in bacteria

Filkov Gleb I. 3
Deyneka Ekaterina V. 3
Bezrukov Dmitry S. 2
Sofronova Alina A. 4
Yamidanov Renat S. 5
Terentiev Victor A. 5
Тип документаJournal Article
Дата публикации2020-01-01
ИздательBentham Science
Название журналаAnti-Infective Agents
Квартиль по SCImagoQ4
Квартиль по Web of Science
Импакт-фактор 2021
ISSN22113525, 22113533
Pharmacology
Infectious Diseases
Краткое описание
Background:

High-throughput screening (HTS) of large-compound libraries is a convenient and cost-effective tool for novel drug discovery. However, in many cases, HTS platforms are not well adapted to perform cell-based screening assay with simultaneous identification of the mechanism of action for active compounds.

Methods:

Previously, we have described a unique double-reporter system that can be used to reveal compounds having antibacterial activity. This construction is based on two genes of Katushka2S and RFP that encode proteins with different imaging signature. The upregulated expression of the first gene attributes directly to translation inhibition in prokaryotes while the high expression of the second one is unambiguously associated with DNA biosynthesis restriction (SOS-response).

Results:

In the current work, we have applied this system for the identification of novel smallmolecule compounds with antibacterial activity in HTS scale. Compounds were selected from the ChemDiv in-house collection (of total 47K molecules) following the maximum diversity in structure. Based on the obtained results, we have revealed a small series of tetrahydrocarbazole derivatives with antibacterial activity. The hit compound inhibited bacterial growth with a MIC value of 21 μg/ml and blocked DNA biosynthesis. No activity towards translation has been observed. In spite of a relatively moderate potency, as compared to the control sample (erythromycin, MIC=3 μg/ml), this molecule provides good selectivity index (SI>333, HEK239).

Conclusion:

Tetrahydrocarbazole derivatives can be properly regarded as an attractive starting point for further development and optimization.

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ГОСТ |
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1. Ivanenkov Y.A. и др. Tetrahydrocarbazoles as Novel Class of DNA Biosynthesis Inhibitors in Bacteria // Anti-Infective Agents. 2020. Т. 18. № 2. С. 121–127.
RIS |
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TY - JOUR

DO - 10.2174/2211352517666181218155259

UR - http://dx.doi.org/10.2174/2211352517666181218155259

TI - Tetrahydrocarbazoles as Novel Class of DNA Biosynthesis Inhibitors in Bacteria

T2 - Anti-Infective Agents

AU - Ivanenkov, Yan A.

AU - Osterman, Ilya A.

AU - Komarova, Ekaterina S.

AU - Bogdanov, Alexey A.

AU - Sergiev, Petr V.

AU - Dontsova, Olga A.

AU - Sofronova, Alina A.

AU - Terentiev, Victor A.

AU - Filkov, Gleb I.

AU - Yamidanov, Renat S.

AU - Majouga, Alexander G.

AU - Bezrukov, Dmitry S.

AU - Deyneka, Ekaterina V.

AU - Skvortsov, Dmitry A.

PY - 2020

DA - 2020/06/08

PB - Bentham Science Publishers Ltd.

SP - 121-127

IS - 2

VL - 18

SN - 2211-3525

ER -

BibTex |
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@article{2020,

doi = {10.2174/2211352517666181218155259},

url = {https://doi.org/10.2174%2F2211352517666181218155259},

year = 2020,

month = {jun},

publisher = {Bentham Science Publishers Ltd.},

volume = {18},

number = {2},

pages = {121--127},

author = {Yan A. Ivanenkov and Ilya A. Osterman and Ekaterina S. Komarova and Alexey A. Bogdanov and Petr V. Sergiev and Olga A. Dontsova and Alina A. Sofronova and Victor A. Terentiev and Gleb I. Filkov and Renat S. Yamidanov and Alexander G. Majouga and Dmitry S. Bezrukov and Ekaterina V. Deyneka and Dmitry A. Skvortsov},

title = {Tetrahydrocarbazoles as Novel Class of {DNA} Biosynthesis Inhibitors in Bacteria}

}

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Ivanenkov, Yan A. et al. “Tetrahydrocarbazoles as Novel Class of DNA Biosynthesis Inhibitors in Bacteria.” Anti-Infective Agents 18.2 (2020): 121–127. Crossref. Web.