2-Pyrazol-1-yl-thiazole derivatives as novel highly potent antibacterials

Yan A. Ivanenkov, Renat S. Yamidanov, Ilya A. Osterman, Petr V. Sergiev, Vladimir A. Aladinskiy, Anastasia V. Aladinskaya, Victor A. Terentiev, Mark S. Veselov, Andrey A. Ayginin, Dmitry A. Skvortsov, Katerina S. Komarova, Sergey V. Sadovnikov, Rustam Matniyazov, Alina A. Sofronova, Alexander S. Malyshev, Alexey E. Machulkin, Rostislav A. Petrov, Dmitrii Lukianov, Svetlana Iarovenko, Dmitry S. BezrukovAndrey Kh Baymiev, Olga A. Dontsova

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


The present report describes our efforts to identify new structural classes of compounds having promising antibacterial activity using previously published double-reporter system pDualrep2. This semi-automated high-throughput screening (HTS) platform has been applied to perform a large-scale screen of a diverse small-molecule compound library. We have selected a set of more than 125,000 molecules and evaluated them for their antibacterial activity. On the basis of HTS results, eight compounds containing 2-pyrazol-1-yl-thiazole scaffold exhibited moderate-to-high activity against ΔTolC Escherichia coli. Minimum inhibitory concentration (MIC) values for these molecules were in the range of 0.037–8 μg ml−1. The most active compound 8 demonstrated high antibacterial potency (MIC = 0.037 μg ml−1), that significantly exceed that measured for erythromycin (MIC = 2.5 μg ml−1) and was comparable with the activity of levofloxacin (MIC = 0.016 μg ml−1). Unfortunately, this compound showed only moderate selectivity toward HEK293 eukaryotic cell line. On the contrary, compound 7 was less potent (MIC = 0.8 μg ml−1) but displayed only slight cytotoxicity. Thus, 2-pyrazol-1-yl-thiazoles can be considered as a valuable starting point for subsequent optimization and morphing.

Original languageEnglish
Pages (from-to)827-833
Number of pages7
JournalJournal of Antibiotics
Issue number11
Publication statusPublished - 1 Nov 2019


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