Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents

Activitat antibiòtica; Ribosoma bacterià; Simulacions de dinàmica molecular

Detalles Bibliográficos
Autores: Pavlova, Julia A., Khairullina, Zimfira Z., Tereshchenkov, Andrey G., Nazarov, Pavel A., Lukianov, Dmitrii A., Volynkina, Inna A., Lyakhovich, Alex
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/6802
Acceso en línea:https://hdl.handle.net/11351/6802
http://hdl.handle.net/11351/6802
Access Level:acceso abierto
Palabra clave:Ribosomes
Medicaments - Efectes fisiològics
Medicaments antiinfecciosos - Ús terapèutic
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents
Other subheadings::Other subheadings::/therapeutic use
ORGANISMS::Bacteria
Other subheadings::Other subheadings::/drug effects
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos
Otros calificadores::Otros calificadores::/uso terapéutico
ORGANISMOS::Bacteria
Otros calificadores::Otros calificadores::/efectos de los fármacos
id ES_77cd113f51b88d05aef6acf70d4e8d8b
oai_identifier_str oai:recercat.cat:11351/6802
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
title Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
spellingShingle Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
Pavlova, Julia A.
Ribosomes
Medicaments - Efectes fisiològics
Medicaments antiinfecciosos - Ús terapèutic
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents
Other subheadings::Other subheadings::/therapeutic use
ORGANISMS::Bacteria
Other subheadings::Other subheadings::/drug effects
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos
Otros calificadores::Otros calificadores::/uso terapéutico
ORGANISMOS::Bacteria
Otros calificadores::Otros calificadores::/efectos de los fármacos
title_short Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
title_full Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
title_fullStr Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
title_full_unstemmed Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
title_sort Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents
dc.creator.none.fl_str_mv Pavlova, Julia A.
Khairullina, Zimfira Z.
Tereshchenkov, Andrey G.
Nazarov, Pavel A.
Lukianov, Dmitrii A.
Volynkina, Inna A.
Lyakhovich, Alex
author Pavlova, Julia A.
author_facet Pavlova, Julia A.
Khairullina, Zimfira Z.
Tereshchenkov, Andrey G.
Nazarov, Pavel A.
Lukianov, Dmitrii A.
Volynkina, Inna A.
Lyakhovich, Alex
author_role author
author2 Khairullina, Zimfira Z.
Tereshchenkov, Andrey G.
Nazarov, Pavel A.
Lukianov, Dmitrii A.
Volynkina, Inna A.
Lyakhovich, Alex
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Pavlova JA, Khairullina ZZ] Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia. [Tereshchenkov AG] A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia. [Nazarov PA] A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia. Laboratory of Molecular Genetics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia. [Lukianov DA] Center of Life Sciences, Skolkovo Institute of Science and Technology, 143028 Skolkovo, Russia. [Volynkina IA] School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia. [Lyakhovich A] Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, 630117 Novosibirsk, Russia. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Ribosomes
Medicaments - Efectes fisiològics
Medicaments antiinfecciosos - Ús terapèutic
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents
Other subheadings::Other subheadings::/therapeutic use
ORGANISMS::Bacteria
Other subheadings::Other subheadings::/drug effects
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos
Otros calificadores::Otros calificadores::/uso terapéutico
ORGANISMOS::Bacteria
Otros calificadores::Otros calificadores::/efectos de los fármacos
topic Ribosomes
Medicaments - Efectes fisiològics
Medicaments antiinfecciosos - Ús terapèutic
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents
Other subheadings::Other subheadings::/therapeutic use
ORGANISMS::Bacteria
Other subheadings::Other subheadings::/drug effects
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos
Otros calificadores::Otros calificadores::/uso terapéutico
ORGANISMOS::Bacteria
Otros calificadores::Otros calificadores::/efectos de los fármacos
description Activitat antibiòtica; Ribosoma bacterià; Simulacions de dinàmica molecular
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/6802
http://hdl.handle.net/11351/6802
url https://hdl.handle.net/11351/6802
http://hdl.handle.net/11351/6802
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Antibiotics;10(5)
https://doi.org/10.3390/antibiotics10050489
info:eu-repo/grantAgreement/ES/PE2013-2016/PI17%2F02087
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411148708708352
spelling Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating AgentsPavlova, Julia A.Khairullina, Zimfira Z.Tereshchenkov, Andrey G.Nazarov, Pavel A.Lukianov, Dmitrii A.Volynkina, Inna A.Lyakhovich, AlexRibosomesMedicaments - Efectes fisiològicsMedicaments antiinfecciosos - Ús terapèuticCHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective AgentsOther subheadings::Other subheadings::/therapeutic useORGANISMS::BacteriaOther subheadings::Other subheadings::/drug effectsCOMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciososOtros calificadores::Otros calificadores::/uso terapéuticoORGANISMOS::BacteriaOtros calificadores::Otros calificadores::/efectos de los fármacosActivitat antibiòtica; Ribosoma bacterià; Simulacions de dinàmica molecularActividad antibiótica; Ribosoma bacteriano; Simulaciones de dinámica molecularAntibiotic activity; Bacterial ribosome; Molecular dynamics simulationsIn the current work, in continuation of our recent research, we synthesized and studied new chimeric compounds, including the ribosome-targeting antibiotic chloramphenicol (CHL) and the membrane-penetrating cation triphenylphosphonium (TPP), which are linked by alkyl groups of different lengths. Using various biochemical assays, we showed that these CAM-Cn-TPP compounds bind to the bacterial ribosome, inhibit protein synthesis in vitro and in vivo in a way similar to that of the parent CHL, and significantly reduce membrane potential. Similar to CAM-C4-TPP, the mode of action of CAM-C10-TPP and CAM-C14-TPP in bacterial ribosomes differs from that of CHL. By simulating the dynamics of CAM-Cn-TPP complexes with bacterial ribosomes, we proposed a possible explanation for the specificity of the action of these analogs in the translation process. CAM-C10-TPP and CAM-C14-TPP more strongly inhibit the growth of the Gram-positive bacteria, as compared to CHL, and suppress some CHL-resistant bacterial strains. Thus, we have shown that TPP derivatives of CHL are dual-acting compounds targeting both the ribosomes and cellular membranes of bacteria. The TPP fragment of CAM-Cn-TPP compounds has an inhibitory effect on bacteria. Moreover, since the mitochondria of eukaryotic cells possess qualities similar to those of their prokaryotic ancestors, we demonstrate the possibility of targeting chemoresistant cancer cells with these compounds.This research was funded by RFBR [grants 20-04-00873 to N.V.S. (synthesis of analogs, binding assays, in vitro translation), 20-015-00537 to P.A.N. (potential measurement, screening of TolC-containing transporters), and 20-54-76002 to I.A.O. (toeprinting and in vitro translation)], President grant MD 2626.2021.1.4 to I.A.O. (bacteria inhibition assays), grants from the Instituto de Salud Carlos III: PI17/02087 to A.L. (cancer cell proliferation assays) by the Ministry of Science and Higher Education of the Russian Federation [grant FENU-2020-0019 to G.I.M. (molecular dynamics simulations)] and by the Government of the Russian Federation [No. AAAA-A17-117120570004-6 to A.A.B.].MDPIInstitut Català de la Salut[Pavlova JA, Khairullina ZZ] Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia. [Tereshchenkov AG] A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia. [Nazarov PA] A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia. Laboratory of Molecular Genetics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia. [Lukianov DA] Center of Life Sciences, Skolkovo Institute of Science and Technology, 143028 Skolkovo, Russia. [Volynkina IA] School of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia. [Lyakhovich A] Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, 630117 Novosibirsk, Russia. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202220222021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/6802http://hdl.handle.net/11351/6802Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésAntibiotics;10(5)https://doi.org/10.3390/antibiotics10050489info:eu-repo/grantAgreement/ES/PE2013-2016/PI17%2F02087Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/68022026-05-29T05:05:01Z
score 15,812429

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