Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents
In order to obtain antimicrobial compounds with improved properties, new conjugates comprising two different biologically active agents within a single chimeric molecule based on chloramphenicol (CHL) and a hydrophobic cation were synthesized and studied. Chloramphenicol amine (CAM), derived from th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/1/15 |
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| author | Julia A. Pavlova Andrey G. Tereshchenkov Pavel A. Nazarov Dmitrii A. Lukianov Dmitry A. Skvortsov Vladimir I. Polshakov Byasilya F. Vasilieva Olga V. Efremenkova Mikhail Y. Kaiumov Alena Paleskava Andrey L. Konevega Olga A. Dontsova Ilya A. Osterman Alexey A. Bogdanov Natalia V. Sumbatyan |
| author_facet | Julia A. Pavlova Andrey G. Tereshchenkov Pavel A. Nazarov Dmitrii A. Lukianov Dmitry A. Skvortsov Vladimir I. Polshakov Byasilya F. Vasilieva Olga V. Efremenkova Mikhail Y. Kaiumov Alena Paleskava Andrey L. Konevega Olga A. Dontsova Ilya A. Osterman Alexey A. Bogdanov Natalia V. Sumbatyan |
| author_sort | Julia A. Pavlova |
| collection | DOAJ |
| description | In order to obtain antimicrobial compounds with improved properties, new conjugates comprising two different biologically active agents within a single chimeric molecule based on chloramphenicol (CHL) and a hydrophobic cation were synthesized and studied. Chloramphenicol amine (CAM), derived from the ribosome-targeting antibiotic CHL, and the plant isoquinoline alkaloid berberine (BER) are connected by alkyl linkers of different lengths in structures of these conjugates. Using competition binding, double reporter system, and toeprinting assays, we showed that synthesized CAM-Cn-BER compounds bound to the bacterial ribosome and inhibited protein synthesis like the parent CHL. The mechanism of action of CAM-C5-BER and CAM-C8-BER on the process of bacterial translations was similar to CHL. Experiments with bacteria demonstrated that CAM-Cn-BERs suppressed the growth of laboratory strains of CHL and macrolides-resistant bacteria. CAM-C8-BER acted against mycobacteria and more selectively inhibited the growth of Gram-positive bacteria than the parent CHL and the berberine derivative lacking the CAM moiety (CH<sub>3</sub>-C8-BER). Using a potential-sensitive fluorescent probe, we found that CAM-C8-BER significantly reduced the membrane potential in <i>B. subtilis</i> cells. Crystal violet assays were used to demonstrate the absence of induction of biofilm formation under the action of CAM-C8-BER on <i>E. coli</i> bacteria. Thus, we showed that CAM-C8-BER could act both on the ribosome and on the cell membrane of bacteria, with the alkylated berberine fragment of the compound making a significant contribution to the inhibitory effect on bacterial growth. Moreover, we showed that CAM-Cn-BERs did not inhibit eukaryotic translation in vitro and were non-toxic for eukaryotic cells. |
| first_indexed | 2024-03-09T13:48:21Z |
| format | Article |
| id | doaj.art-a605ba928b33422cadcd2b7d2d8bc6a5 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T13:48:21Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | Antibiotics |
| spelling | doaj.art-a605ba928b33422cadcd2b7d2d8bc6a52023-11-30T20:54:32ZengMDPI AGAntibiotics2079-63822022-12-011211510.3390/antibiotics12010015Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial AgentsJulia A. Pavlova0Andrey G. Tereshchenkov1Pavel A. Nazarov2Dmitrii A. Lukianov3Dmitry A. Skvortsov4Vladimir I. Polshakov5Byasilya F. Vasilieva6Olga V. Efremenkova7Mikhail Y. Kaiumov8Alena Paleskava9Andrey L. Konevega10Olga A. Dontsova11Ilya A. Osterman12Alexey A. Bogdanov13Natalia V. Sumbatyan14Department of Chemistry, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1/40 Leninskie Gory, 119992 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1/40 Leninskie Gory, 119992 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaFaculty of Fundamental Medicine, Lomonosov Moscow State University, 27/1 Lomonosvsky Ave., 119991 Moscow, RussiaGause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, RussiaGause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, RussiaPetersburg Nuclear Physics Institute, NRC “Kurchatov Institute”, 188300 Gatchina, RussiaPetersburg Nuclear Physics Institute, NRC “Kurchatov Institute”, 188300 Gatchina, RussiaPetersburg Nuclear Physics Institute, NRC “Kurchatov Institute”, 188300 Gatchina, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 1/3 Leninskie Gory, 119991 Moscow, RussiaIn order to obtain antimicrobial compounds with improved properties, new conjugates comprising two different biologically active agents within a single chimeric molecule based on chloramphenicol (CHL) and a hydrophobic cation were synthesized and studied. Chloramphenicol amine (CAM), derived from the ribosome-targeting antibiotic CHL, and the plant isoquinoline alkaloid berberine (BER) are connected by alkyl linkers of different lengths in structures of these conjugates. Using competition binding, double reporter system, and toeprinting assays, we showed that synthesized CAM-Cn-BER compounds bound to the bacterial ribosome and inhibited protein synthesis like the parent CHL. The mechanism of action of CAM-C5-BER and CAM-C8-BER on the process of bacterial translations was similar to CHL. Experiments with bacteria demonstrated that CAM-Cn-BERs suppressed the growth of laboratory strains of CHL and macrolides-resistant bacteria. CAM-C8-BER acted against mycobacteria and more selectively inhibited the growth of Gram-positive bacteria than the parent CHL and the berberine derivative lacking the CAM moiety (CH<sub>3</sub>-C8-BER). Using a potential-sensitive fluorescent probe, we found that CAM-C8-BER significantly reduced the membrane potential in <i>B. subtilis</i> cells. Crystal violet assays were used to demonstrate the absence of induction of biofilm formation under the action of CAM-C8-BER on <i>E. coli</i> bacteria. Thus, we showed that CAM-C8-BER could act both on the ribosome and on the cell membrane of bacteria, with the alkylated berberine fragment of the compound making a significant contribution to the inhibitory effect on bacterial growth. Moreover, we showed that CAM-Cn-BERs did not inhibit eukaryotic translation in vitro and were non-toxic for eukaryotic cells.https://www.mdpi.com/2079-6382/12/1/15chloramphenicolberberineC-13 derivatives of berberinebacterial ribosomebacterial membrane potentialantibiotic activity |
| spellingShingle | Julia A. Pavlova Andrey G. Tereshchenkov Pavel A. Nazarov Dmitrii A. Lukianov Dmitry A. Skvortsov Vladimir I. Polshakov Byasilya F. Vasilieva Olga V. Efremenkova Mikhail Y. Kaiumov Alena Paleskava Andrey L. Konevega Olga A. Dontsova Ilya A. Osterman Alexey A. Bogdanov Natalia V. Sumbatyan Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents Antibiotics chloramphenicol berberine C-13 derivatives of berberine bacterial ribosome bacterial membrane potential antibiotic activity |
| title | Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents |
| title_full | Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents |
| title_fullStr | Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents |
| title_full_unstemmed | Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents |
| title_short | Conjugates of Chloramphenicol Amine and Berberine as Antimicrobial Agents |
| title_sort | conjugates of chloramphenicol amine and berberine as antimicrobial agents |
| topic | chloramphenicol berberine C-13 derivatives of berberine bacterial ribosome bacterial membrane potential antibiotic activity |
| url | https://www.mdpi.com/2079-6382/12/1/15 |
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