Antibacterial activity of noscapine analogs.

Autor: Ivanenkov YA; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia; The Federal State Unitary Enterprise Dukhov Automatics Research Institute, Moscow 127055, Russia. Electronic address: yaiivanenkov@gmail.com., Yu Filyaeva K; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia; Bashkir State Medical University, Ministry of Health of Russia, Ufa 450008, Russia., Matniyazov RT; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia., Baymiev AK; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia; Bashkir State Medical University, Ministry of Health of Russia, Ufa 450008, Russia., Baymiev AK; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia; Bashkir State Medical University, Ministry of Health of Russia, Ufa 450008, Russia., Vladimirova AA; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia., Yamidanov RS; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia., Mavzyutov AR; Bashkir State Medical University, Ministry of Health of Russia, Ufa 450008, Russia., Zileeva ZR; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia., Zainullina LF; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia., Vakhitova JV; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia., Marina VI; Department of Chemistry and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia., Terentiev VA; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa Scientific Centre, Ufa 450054, Russia; Department of Chemistry, Lomonosov Moscow State University, Moscow 119234, Russia., Osterman IA; Department of Chemistry and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia; Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143026, Russia., Kartsev VG; InterBioScreen ltd, Chernogolovka 142432, Russia., Bezrukov DS; Department of Chemistry, Lomonosov Moscow State University, Moscow 119234, Russia., Dontsova OA; Department of Chemistry and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia; Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143026, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 142290, Russia.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2021 Jul 01; Vol. 43, pp. 128055. Date of Electronic Publication: 2021 Apr 21.
DOI: 10.1016/j.bmcl.2021.128055
Abstrakt: The antibacterial properties of close noscapine analogs have not been previously reported. We used our pDualrep2 double-reporter High Throughput Screening (HTS) platform to identify a series of noscapine derivatives with promising antibacterial activity. The platform is based on RPF (SOS-response/DNA damage) and Katushka2S (inhibition of translation) proteins and simultaneously provides information on antibacterial activity and the mechanism of action of small-molecule compounds against E. coli. The most potent compound exhibited an MIC of 13.5 µM(6.25 µg/ml) and a relatively low cytotoxicity against HEK293 cells (CC 50  = 71 µM, selectivity index: ~5.5). Some compounds from this series induced average Katushka2S reporter signals, indicating inhibition of translation machinery in the bacteria; however, these compounds did not attenuate translation in vitro in a luciferase-based translation assay. The most effective compounds did not significantly arrest the mitotic cycle in HEK293 cells, in contrast to the parent compound in a flow cytometry assay. Several molecules showed activity against clinically relevant gram-negative and gram-positive bacterial strains. Compounds from the discovered series can be reasonably regarded as good templates for further development and evaluation.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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