Combinatorial Chemistry and High Throughput Screening, том 22, издание 5, номера страниц: 346-354

Identification of n-substituted triazolo-azetidines as novel antibacterials using pdualrep2 HTS platform

Filkov Gleb I. 4
Machulkin Alexey E. 1
Aladinskiy Vladimir A. 2
Ayginin Andrey A. 5
Petrov Rostislav A. 1
Veselov Mark S. 5
Bezrukov Dmitry S. 1
Puchinina Maria M. 4
Sofronova Alina A. 6
Malyshev Alexander S. 7
Yamidanov Renat S. 5
Terentiev Victor A. 5
Chemeris Alexey V. 5
Baimiev Alexey Kh. 5
Maximova Marina A. 5
Zileeva Zulfiya R. 5
Vakhitova Yulia V. 5
Тип документаJournal Article
Дата публикации2019-01-01
ИздательBentham Science
Название журналаCombinatorial Chemistry and High Throughput Screening
Квартиль по SCImagoQ4
Квартиль по Web of ScienceQ3
Импакт-фактор 20211.71
ISSN13862073, 18755402
Organic Chemistry
Drug Discovery
Computer Science Applications
General Medicine
Краткое описание
Aim and Objective:

Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity.

Materials and Methods:

Using our unique double-reporter system, in-house large-scale HTS campaign was conducted for the identification of antibacterial potency of small-molecule compounds. The construction allows us to visually assess the underlying mechanism of action. After the initial HTS and rescreen procedure, luciferase assay, C14-test, determination of MIC value and PrestoBlue test were carried out.


HTS rounds and rescreen campaign have revealed the antibacterial activity of a series of Nsubstituted triazolo-azetidines and their isosteric derivatives that has not been reported previously. Primary hit-molecule demonstrated a MIC value of 12.5 µg/mL against E. coli Δ tolC with signs of translation blockage and no SOS-response. Translation inhibition (26%, luciferase assay) was achieved at high concentrations up to 160 µg/mL, while no activity was found using C14-test. The compound did not demonstrate cytotoxicity in the PrestoBlue assay against a panel of eukaryotic cells. Within a series of direct structural analogues bearing the same or bioisosteric scaffold, compound 2 was found to have an improved antibacterial potency (MIC=6.25 µg/mL) close to Erythromycin (MIC=2.5-5 µg/mL) against the same strain. In contrast to the parent hit, this compound was more active and selective, and provided a robust IP position.


N-substituted triazolo-azetidine scaffold may be used as a versatile starting point for the development of novel active and selective antibacterial compounds.

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1. Ivanenkov Y.A. и др. Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using pDualrep2 HTS Platform // Combinatorial Chemistry & High Throughput Screening. 2019. Т. 22. № 5. С. 346–354.


DO - 10.2174/1386207322666190412165316

UR -

TI - Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using pDualrep2 HTS Platform

T2 - Combinatorial Chemistry & High Throughput Screening

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 - Chemeris, Alexey V.

AU - Baimiev, Alexey Kh.

AU - Sofronova, Alina A.

AU - Malyshev, Alexander S.

AU - Machulkin, Alexey E.

AU - Petrov, Rostislav A.

AU - Bezrukov, Dmitry S.

AU - Filkov, Gleb I.

AU - Puchinina, Maria M.

AU - Zainullina, Liana F.

AU - Maximova, Marina A.

AU - Zileeva, Zulfiya R.

AU - Vakhitova, Yulia V.

AU - Dontsova, Olga A.

PY - 2019

DA - 2019/08/08

PB - Bentham Science Publishers Ltd.

SP - 346-354

IS - 5

VL - 22

SN - 1386-2073

ER -

BibTex |


doi = {10.2174/1386207322666190412165316},

url = {},

year = 2019,

month = {aug},

publisher = {Bentham Science Publishers Ltd.},

volume = {22},

number = {5},

pages = {346--354},

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 Alexey V. Chemeris and Alexey Kh. Baimiev and Alina A. Sofronova and Alexander S. Malyshev and Alexey E. Machulkin and Rostislav A. Petrov and Dmitry S. Bezrukov and Gleb I. Filkov and Maria M. Puchinina and Liana F. Zainullina and Marina A. Maximova and Zulfiya R. Zileeva and Yulia V. Vakhitova and Olga A. Dontsova},

title = {Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using {pDualrep}2 {HTS} Platform}


Ivanenkov, Yan A. et al. “Identification of N-Substituted Triazolo-Azetidines as Novel Antibacterials Using pDualrep2 HTS Platform.” Combinatorial Chemistry & High Throughput Screening 22.5 (2019): 346–354. Crossref. Web.