Open Access
Anti-Infective Agents, volume 18, issue 2, pages 121-127
Tetrahydrocarbazoles as novel class of DNA biosynthesis inhibitors in bacteria
Ivanenkov Yan A
1
,
Osterman Ilya A.
2
,
Bogdanov Alexey A.
2
,
Sergiev Petr V.
2
,
Dontsova Olga A.
2
,
Sofronova Alina A.
3
,
Terentiev Victor A.
4
,
Filkov Gleb I.
1
,
Yamidanov Renat S.
4
,
Bezrukov Dmitry S.
5
,
Deyneka Ekaterina V.
1
,
3
Lomonosov Moscow, Faculty of Bioengineering and Bioinformatics, State University, Moscow, Russian Federation
|
4
5
Lomonosov Moscow, Chemistry Department, State University, Moscow, Russian Federation
|
Publication type: Journal Article
Publication date: 2020-06-08
Journal:
Anti-Infective Agents
Quartile SCImago
Q4
Quartile WOS
—
Impact factor: —
ISSN: 22113525, 22113533
Pharmacology
Infectious Diseases
Abstract
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.
Citations by journals
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1
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Chinese Chemical Letters
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Chinese Chemical Letters
1 publication, 25%
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Journal of Organic Chemistry
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Journal of Organic Chemistry
1 publication, 25%
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European Journal of Medicinal Chemistry
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European Journal of Medicinal Chemistry
1 publication, 25%
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European Journal of Chemistry
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European Journal of Chemistry, 1, 25%
European Journal of Chemistry
1 publication, 25%
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1
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Citations by publishers
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1
2
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Elsevier
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Elsevier
2 publications, 50%
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American Chemical Society (ACS)
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American Chemical Society (ACS)
1 publication, 25%
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European Journal of Chemistry
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European Journal of Chemistry, 1, 25%
European Journal of Chemistry
1 publication, 25%
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1
2
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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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.
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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://doi.org/10.2174%2F2211352517666181218155259
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 00:00:00
PB - Bentham Science
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},
month = {jun},
url = {https://doi.org/10.2174%2F2211352517666181218155259},
number = {2},
pages = {121--127},
doi = {10.2174/2211352517666181218155259}
}
Cite this
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://doi.org/10.2174%2F2211352517666181218155259.