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

Pavlova, J.A.; Khairullina, Z.Z.; Tereshchenkov, A.G.; Nazarov, P.A.; Lukianov, D.A.; Volynkina, I.A.; Skvortsov, D.A.; Makarov, G.I.; Abad, E.; Murayama, S.Y.; Kajiwara, S.; Paleskava, A.; Konevega, A.L.; Antonenko, Y.N.; Lyakhovich, A.; Osterman, I.A.; Bogdanov, A.A.; Sumbatyan, N.V.

Авторы: Pavlova Julia A., Khairullina Zimfira Z., Tereshchenkov Andrey G., Nazarov Pavel A., Lukianov Dmitrii A., Volynkina Inna A., Skvortsov Dmitry A., Makarov Gennady I., Abad Etna, Murayama Somay Y., Kajiwara Susumu, Paleskava Alena, Konevega Andrey L., Antonenko Yuri N., Lyakhovich Alex, Osterman Ilya A., Bogdanov Alexey A., Sumbatyan Natalia V.
Журнал: Antibiotics
Том: 10
Номер: 5
Год издания: 2021
Издательство: MDPI Publishing
Местоположение издательства: Basel, Switzerland, Switzerland
Первая страница: 489
Последняя страница: 511
DOI: 10.3390/antibiotics10050489
Аннотация: In the current work, in continuation of our recent research, we synthesized and studiednew chimeric compounds, including the ribosome-targeting antibiotic chloramphenicol (CHL) andthe membrane-penetrating cation triphenylphosphonium (TPP), which are linked by alkyl groups ofdifferent lengths. Using various biochemical assays, we showed that these CAM-Cn-TPP compoundsbind to the bacterial ribosome, inhibit protein synthesis in vitro and in vivo in a way similar tothat of the parent CHL, and significantly reduce membrane potential. Similar to CAM-C4-TPP, themode 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 proposeda 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 shownthat TPP derivatives of CHL are dual-acting compounds targeting both the ribosomes and cellularmembranes of bacteria. The TPP fragment of CAM-Cn-TPP compounds has an inhibitory effect onbacteria. Moreover, since the mitochondria of eukaryotic cells possess qualities similar to those oftheir prokaryotic ancestors, we demonstrate the possibility of targeting chemoresistant cancer cellswith these compounds.
Добавил в систему: Павлова Юлия Анатольевна

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

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