Substituted Furanocoumarins as Novel Class of Antibacterial Translation Inhibitors.

Autor:	Ivanenkov YA; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation.; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation.; Lomonosov Moscow State University, Chemistry Dept, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation.; ChemDiv, 6605 Nancy Ridge Drive, San Diego, CA 92121, United States., Yamidanov RS; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation., Osterman IA; Lomonosov Moscow State University, Chemistry Dept, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation., Sergiev PV; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation.; Lomonosov Moscow State University, Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russian Federation., Ayginin AA; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation.; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation., Aladinskiy VA; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation., Aladinskaya AV; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation., Terentiev VA; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation.; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation.; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation., Veselov MS; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation.; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation.; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation., Skvortsov DA; Lomonosov Moscow State University, Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russian Federation., Komarova KS; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation.; Lomonosov Moscow State University, Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russian Federation., Chemeris AV; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation., Zainullina LF; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation., Maximova MA; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation., Zileeva ZR; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation., Vakhitova YV; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation., Baymiev AK; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation., Baymiev AK; Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS) Ufa Scientific Centre, Oktyabrya Prospekt 71, 450054, Ufa, Russian Federation., Sofronova AA; Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, Russian Federation., Machulkin AE; Lomonosov Moscow State University, Chemistry Dept, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Petrov RA; Lomonosov Moscow State University, Chemistry Dept, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation., Bezrukov DS; Lomonosov Moscow State University, Chemistry Dept, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation., Puchinina MM; Moscow Institute of Physics and Technology (State University), 9 Institutskiy lane, Dolgoprudny City, Moscow Region 141700, Russian Federation., Lukianov DA; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation., Dontsova OA; Lomonosov Moscow State University, Chemistry Dept, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian Federation.; Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation.; Lomonosov Moscow State University, Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow, Russian Federation.
Jazyk:	angličtina
Zdroj:	Combinatorial chemistry & high throughput screening [Comb Chem High Throughput Screen] 2019; Vol. 22 (6), pp. 400-410.
DOI:	10.2174/1386207322666190723110539
Abstrakt:	Introduction: A variety of organic compounds has been reported to have antibacterial activity. However, antimicrobial resistance is one of the main problems of current anti-infective therapy, and the development of novel antibacterials is one of the main challenges of current drug discovery. Methods: Using our previously developed dual-reporter High-Throughput Screening (HTS) platform, we identified a series of furanocoumarins as having high antibacterial activity. The construction of the reporter system allows us to differentiate three mechanisms of action for the active compounds: inhibition of protein synthesis (induction of Katushka2S), DNA damaging (induction of RFP) or other (inhibition of bacterial growth without reporter induction). Results: Two primary hit-molecules of furanocoumarin series demonstrated relatively low MIC values comparable to that observed for Erythromycin (Ery) against E. coli and weakly induced both reporters. Dose-dependent translation inhibition was shown using in vitro luciferase assay, however it was not confirmed using C14-test. A series of close structure analogs of the identified hits was obtained and investigated using the same screening platform. Compound 19 was found to have slightly lower MIC value (15.18 µM) and higher induction of Katushka2S reporter in contrast to the parent structures. Moreover, translation blockage was clearly identified using both in vitro luciferase assay and C14 test. The standard cytotoxicity test revealed a relatively low cytotoxicity of the most active molecules. Conclusion: High antibacterial activity in combination with low cytotoxicity was demonstrated for a series of furanocoumarins. Further optimization of the described structures may result in novel and attractive lead compounds with promising antibacterial efficiency. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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