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Bentham Science Publishers Ltd.
Anti-Infective Agents
,  том 18 ,  издание 2 ,  страницы 121-127

Tetrahydrocarbazoles as novel class of DNA biosynthesis inhibitors in bacteria

Yan A Ivanenkov 1
, 
Ilya A. Osterman 2
, 
Ekaterina S. Komarova 3
, 
Alexey A. Bogdanov 2
, 
Petr V. Sergiev 2
, 
Olga A. Dontsova 2
, 
Alina A. Sofronova 3
, 
Victor A. Terentiev 4
, 
Gleb I. Filkov 1
, 
Renat S. Yamidanov 4
, 
Alexander G. Majouga 2
, 
Dmitry S. Bezrukov 5
, 
Ekaterina V. Deyneka 1
, 
Dmitry A. Skvortsov 5
1
 
2
 
3
 
Lomonosov Moscow, Faculty of Bioengineering and Bioinformatics, State University, Moscow, Russian Federation | 
4
 
5
 
Lomonosov Moscow, Chemistry Department, State University, Moscow, Russian Federation | 
Тип публикации: Journal Article
Дата публикации: 2020-06-08
Bentham Science Publishers Ltd.
scimago Q4
БС3
SJR: 0.167
CiteScore: 1.3
Impact factor: —
ISSN: 22113525, 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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Ivanenkov Y. A. et al. Tetrahydrocarbazoles as novel class of DNA biosynthesis inhibitors in bacteria // Anti-Infective Agents. 2020. Vol. 18. No. 2. pp. 121-127.
ГОСТ со всеми авторами (до 50) Скопировать
Ivanenkov Y. A., Osterman I. A., Komarova E. S., Bogdanov A. A., Sergiev P. V., Dontsova O. A., Sofronova A. A., Terentiev V. A., Filkov G. I., Yamidanov R. S., Majouga A. G., Bezrukov D. S., Deyneka E. V., Skvortsov D. A. Tetrahydrocarbazoles as novel class of DNA biosynthesis inhibitors in bacteria // Anti-Infective Agents. 2020. Vol. 18. No. 2. pp. 121-127.
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TY - JOUR
DO - 10.2174/2211352517666181218155259
UR - https://www.eurekaselect.com/168431/article
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
SN - 2211-3533
ER -
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@article{2020_Ivanenkov,
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},
journal = {Anti-Infective Agents},
year = {2020},
volume = {18},
publisher = {Bentham Science Publishers Ltd.},
month = {jun},
url = {https://www.eurekaselect.com/168431/article},
number = {2},
pages = {121--127},
doi = {10.2174/2211352517666181218155259}
}
MLA
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Ivanenkov, Yan A., et al. “Tetrahydrocarbazoles as novel class of DNA biosynthesis inhibitors in bacteria.” Anti-Infective Agents, vol. 18, no. 2, Jun. 2020, pp. 121-127. https://www.eurekaselect.com/168431/article.