Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains

Structurally unrelated antibiotics MLS(B) (macrolide-lincosamide-streptogramin B) compromised with clinically resistant pathogens because of the cross-resistance resulting from the structural modification of rRNA A2058. The structure–activity relationships of a novel 3-O-descladinose azithromycin ch...

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Autores principales: Lian, Xiaotian, Liu, Wentian, Fan, Bingzhi, Yu, Mingjia, Liang, Jianhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9920417/
https://www.ncbi.nlm.nih.gov/pubmed/36770992
http://dx.doi.org/10.3390/molecules28031327
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author Lian, Xiaotian
Liu, Wentian
Fan, Bingzhi
Yu, Mingjia
Liang, Jianhua
author_facet Lian, Xiaotian
Liu, Wentian
Fan, Bingzhi
Yu, Mingjia
Liang, Jianhua
author_sort Lian, Xiaotian
collection PubMed
description Structurally unrelated antibiotics MLS(B) (macrolide-lincosamide-streptogramin B) compromised with clinically resistant pathogens because of the cross-resistance resulting from the structural modification of rRNA A2058. The structure–activity relationships of a novel 3-O-descladinose azithromycin chemotype conjugating with nucleobases were fully explored with the aid of engineered E. coli SQ110DTC and SQ110LPTD. The conjugates of macrolides with nucleobases, especially adenine, displayed antibacterial superiority over telithromycin, azithromycin and clindamycin against rRNA A2058/2059-mutated engineered E. coli strains at the cost of lowering permeability and increasing vulnerability to efflux proteins against clinical isolates.
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spelling pubmed-99204172023-02-12 Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains Lian, Xiaotian Liu, Wentian Fan, Bingzhi Yu, Mingjia Liang, Jianhua Molecules Article Structurally unrelated antibiotics MLS(B) (macrolide-lincosamide-streptogramin B) compromised with clinically resistant pathogens because of the cross-resistance resulting from the structural modification of rRNA A2058. The structure–activity relationships of a novel 3-O-descladinose azithromycin chemotype conjugating with nucleobases were fully explored with the aid of engineered E. coli SQ110DTC and SQ110LPTD. The conjugates of macrolides with nucleobases, especially adenine, displayed antibacterial superiority over telithromycin, azithromycin and clindamycin against rRNA A2058/2059-mutated engineered E. coli strains at the cost of lowering permeability and increasing vulnerability to efflux proteins against clinical isolates. MDPI 2023-01-30 /pmc/articles/PMC9920417/ /pubmed/36770992 http://dx.doi.org/10.3390/molecules28031327 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lian, Xiaotian
Liu, Wentian
Fan, Bingzhi
Yu, Mingjia
Liang, Jianhua
Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains
title Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains
title_full Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains
title_fullStr Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains
title_full_unstemmed Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains
title_short Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains
title_sort design, synthesis and biological evaluation of conjugates of 3-o-descladinose-azithromycin and nucleobases against rrna a2058g- or a2059g-mutated strains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9920417/
https://www.ncbi.nlm.nih.gov/pubmed/36770992
http://dx.doi.org/10.3390/molecules28031327
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