Current Drug Discovery Technologies, том 17, издание 5, номера страниц: 716-724

Large-scale high-throughput screening revealed 5'-(carbonylamino)-2,3'- bithiophene-4'-carboxylate as novel template for antibacterial agents

Machulkin Alexey E. 1
Aladinskiy Vladimir A. 4
Ayginin Andrey A. 5
Petrov Rostislav A. 1
Veselov Mark S. 5
Bezrukov Dmitry S. 1
Puchinina Maria M. 4
Sofronova Alina A. 6
Yamidanov Renat S. 5
Terentiev Victor A. 5
Komarova Katerina S. 3
Baimiev Alexey Kh. 5
Maximova Marina A. 5
Zileeva Zulfiya R. 5
Vakhitova Yulia V. 5
Zagribelnyy Bogdan A. 1
Shvetc Kseniya Yu. 5
Baimiev Andrey Kh. 5
Тип документаJournal Article
Дата публикации2020-01-01
ИздательBentham Science
Название журналаCurrent Drug Discovery Technologies
Квартиль по SCImagoQ4
Квартиль по Web of Science
Импакт-фактор 2021
Drug Discovery
Краткое описание

The key issue in the development of novel antimicrobials is a rapid expansion of new bacterial strains resistant to current antibiotics. Indeed, World Health Organization has reported that bacteria commonly causing infections in hospitals and in the community, e.g. E. Coli, K. pneumoniae and S. aureus, have high resistance vs the last generations of cephalosporins, carbapenems and fluoroquinolones. During the past decades, only few successful efforts to develop and launch new antibacterial medications have been performed. This study aims to identify new class of antibacterial agents using novel high-throughput screening technique.


We have designed library containing 125K compounds not similar in structure (Tanimoto coeff.< 0.7) to that published previously as antibiotics. The HTS platform based on double reporter system pDualrep2 was used to distinguish between molecules able to block translational machinery or induce SOS-response in a model E. coli system. MICs for most active chemicals in LB and M9 medium were determined using broth microdilution assay.


In an attempt to discover novel classes of antibacterials, we performed HTS of a large-scale small molecule library using our unique screening platform. This approach permitted us to quickly and robustly evaluate a lot of compounds as well as to determine the mechanism of action in the case of compounds being either translational machinery inhibitors or DNA-damaging agents/replication blockers. HTS has resulted in several new structural classes of molecules exhibiting an attractive antibacterial activity. Herein, we report as promising antibacterials. Two most active compounds from this series showed MIC value of 1.2 (5) and 1.8 μg/mL (6) and good selectivity index. Compound 6 caused RFP induction and low SOS response. In vitro luciferase assay has revealed that it is able to slightly inhibit protein biosynthesis. Compound 5 was tested on several archival strains and exhibited slight activity against gram-negative bacteria and outstanding activity against S. aureus. The key structural requirements for antibacterial potency were also explored. We found, that the unsubstituted carboxylic group is crucial for antibacterial activity as well as the presence of bulky hydrophobic substituents at phenyl fragment.


The obtained results provide a solid background for further characterization of the 5'- (carbonylamino)-2,3'-bithiophene-4'-carboxylate derivatives discussed herein as new class of antibacterials and their optimization campaign.

Цитируется в публикациях: 1


1. Ivanenkov Y.A. и др. Large-scale High-throughput Screening Revealed 5’-(carbonylamino)-2,3’- bithiophene-4’-carboxylate as Novel Template for Antibacterial Agents // Current Drug Discovery Technologies. 2020. Т. 17. № 5. С. 716–724.


DO - 10.2174/1570163816666190603095521

UR -

TI - Large-scale High-throughput Screening Revealed 5'-(carbonylamino)-2,3'- bithiophene-4'-carboxylate as Novel Template for Antibacterial Agents

T2 - Current Drug Discovery Technologies

AU - Ivanenkov, Yan A.

AU - Yamidanov, Renat S.

AU - Osterman, Ilya A.

AU - Sergiev, Petr V.

AU - Aladinskiy, Vladimir A.

AU - Aladinskaya, Anastasia V.

AU - Terentiev, Victor A.

AU - Veselov, Mark S.

AU - Ayginin, Andrey A.

AU - Skvortsov, Dmitry A.

AU - Komarova, Katerina S.

AU - Zagribelnyy, Bogdan A.

AU - Baimiev, Alexey Kh.

AU - Shvetc, Kseniya Yu.

AU - Baimiev, Andrey Kh.

AU - Sofronova, Alina A.

AU - Machulkin, Alexey E.

AU - Petrov, Rostislav A.

AU - Zainullina, Liana F.

AU - Maximova, Marina A.

AU - Zileeva, Zulfiya R.

AU - Vakhitova, Yulia V.

AU - Bezrukov, Dmitry S.

AU - Puchinina, Maria M.

AU - Dontsova, Olga A.

PY - 2020

DA - 2020/12/23

PB - Bentham Science Publishers Ltd.

SP - 716-724

IS - 5

VL - 17

SN - 1570-1638

ER -

BibTex |


doi = {10.2174/1570163816666190603095521},

url = {},

year = 2020,

month = {dec},

publisher = {Bentham Science Publishers Ltd.},

volume = {17},

number = {5},

pages = {716--724},

author = {Yan A. Ivanenkov and Renat S. Yamidanov and Ilya A. Osterman and Petr V. Sergiev and Vladimir A. Aladinskiy and Anastasia V. Aladinskaya and Victor A. Terentiev and Mark S. Veselov and Andrey A. Ayginin and Dmitry A. Skvortsov and Katerina S. Komarova and Bogdan A. Zagribelnyy and Alexey Kh. Baimiev and Kseniya Yu. Shvetc and Andrey Kh. Baimiev and Alina A. Sofronova and Alexey E. Machulkin and Rostislav A. Petrov and Liana F. Zainullina and Marina A. Maximova and Zulfiya R. Zileeva and Yulia V. Vakhitova and Dmitry S. Bezrukov and Maria M. Puchinina and Olga A. Dontsova},

title = {Large-scale High-throughput Screening Revealed 5{\textquotesingle}-(carbonylamino)-2,3{\textquotesingle}- bithiophene-4{\textquotesingle}-carboxylate as Novel Template for Antibacterial Agents}


Ivanenkov, Yan A. et al. “Large-Scale High-Throughput Screening Revealed 5’-(carbonylamino)-2,3’- Bithiophene-4’-Carboxylate as Novel Template for Antibacterial Agents.” Current Drug Discovery Technologies 17.5 (2020): 716–724. Crossref. Web.