N-Pyridyl-Substituted Carboxypiperidine Amides: A New Class of Prokaryote Translation Inhibitors


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Abstract

High-throughput screening identified a new class of antibacterial compounds based on N-pyridyl-substituted p- and m-carboxypiperidine amides. Constructs with the two reporter genes RFP and Katushka2S allowed the detection of compounds that inhibit protein translation against DNA biosynthesis. Some agents of this class demonstrated antibacterial activity by inhibiting translation. The most promising compound had an MIC of 12 μg/mL. Thus, this class could become a valuable platform for developing new compounds with higher antibacterial activity and selectivity.

About the authors

Ya. A. Ivanenkov

Moscow Institute of Physics and Technology (State University); Department of Chemistry, M. V. Lomonosov Moscow State University; Institute of Biochemistry and Genetics, Ufa Scientific Center, Russian Academy of Sciences

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 9 Institutskii Pereul., Moscow Region, Dolgoprudnyi, 141700; 1/3 Leninskie Gory, Moscow, 119991; 71 Prosp. Oktyabrya, Ufa, Republic of Bashkortostan, 450054

E. S. Komarova (Andreyanova)

A. N. Belozersky Research Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 1/40, Leninskie Gory, Moscow, 119992

I. A. Osterman

A. N. Belozersky Research Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 1/40, Leninskie Gory, Moscow, 119992

P. V. Sergiev

A. N. Belozersky Research Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 1/40, Leninskie Gory, Moscow, 119992

R. S. Yamidanov

Institute of Biochemistry and Genetics, Ufa Scientific Center, Russian Academy of Sciences

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 71 Prosp. Oktyabrya, Ufa, Republic of Bashkortostan, 450054

E. V. Deineka

Moscow Institute of Physics and Technology (State University)

Author for correspondence.
Email: ekaterina.deyneka@phystech.edu
Russian Federation, 9 Institutskii Pereul., Moscow Region, Dolgoprudnyi, 141700

V. A. Terent’ev

Institute of Biochemistry and Genetics, Ufa Scientific Center, Russian Academy of Sciences

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 71 Prosp. Oktyabrya, Ufa, Republic of Bashkortostan, 450054

G. I. Fil’kov

Moscow Institute of Physics and Technology (State University)

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 9 Institutskii Pereul., Moscow Region, Dolgoprudnyi, 141700

A. A. Sofronova

Department of Bioengineering and Bioinformatics, M. V. Lomonosov Moscow State University

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 1/73 Leninskie Gory, Moscow, 119234

A. G. Mazhuga

Department of Chemistry, M. V. Lomonosov Moscow State University; National University of Science and Technology Moscow Institute of Steel and Alloys (MISiS); D. I. Mendeleev University of Chemical Technology of Russia

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 1/3 Leninskie Gory, Moscow, 119991; 4 Leninskii Prosp., Moscow, 119049; 9 Miusskaya Sq., Moscow, 125047

O. A. Dontsova

A. N. Belozersky Research Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University

Email: ekaterina.deyneka@phystech.edu
Russian Federation, 1/40, Leninskie Gory, Moscow, 119992


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