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

Xiaotian Lian; Wentian Liu; Bingzhi Fan; Mingjia Yu; Jianhua Liang

doi:10.3390/molecules28031327

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

Xiaotian Lian, Wentian Liu, Bingzhi Fan, Mingjia Yu^*, Jianhua Liang^*

^*Corresponding author for this work

School of Chemistry and Chemical Engineering

Beijing Institute of Technology

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	1327
Journal	Molecules
Volume	28
Issue number	3
DOIs	https://doi.org/10.3390/molecules28031327
Publication status	Published - Feb 2023

Keywords

MLS
SARs
antibiotics
drug design
nucleobase

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10.3390/molecules28031327

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

abstract = "Structurally unrelated antibiotics MLSB (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.",

keywords = "MLS, SARs, antibiotics, drug design, nucleobase",

author = "Xiaotian Lian and Wentian Liu and Bingzhi Fan and Mingjia Yu and Jianhua Liang",

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AU - Lian, Xiaotian

AU - Liu, Wentian

AU - Fan, Bingzhi

AU - Yu, Mingjia

AU - Liang, Jianhua

PY - 2023/2

Y1 - 2023/2

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AB - Structurally unrelated antibiotics MLSB (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.

KW - MLS

KW - SARs

KW - antibiotics

KW - drug design

KW - nucleobase

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U2 - 10.3390/molecules28031327

DO - 10.3390/molecules28031327

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VL - 28

JO - Molecules

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

Abstract

Keywords

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