Design, Synthesis and Biological Evaluation of Conjugates of 3-<i>O</i>-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains
Structurally unrelated antibiotics MLS<sub>B</sub> (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-<i>...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/3/1327 |
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| author | Xiaotian Lian Wentian Liu Bingzhi Fan Mingjia Yu Jianhua Liang |
| author_facet | Xiaotian Lian Wentian Liu Bingzhi Fan Mingjia Yu Jianhua Liang |
| author_sort | Xiaotian Lian |
| collection | DOAJ |
| description | Structurally unrelated antibiotics MLS<sub>B</sub> (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-<i>O</i>-descladinose azithromycin chemotype conjugating with nucleobases were fully explored with the aid of engineered <i>E. coli</i> 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 <i>E. coli</i> strains at the cost of lowering permeability and increasing vulnerability to efflux proteins against clinical isolates. |
| first_indexed | 2024-03-11T09:32:34Z |
| format | Article |
| id | doaj.art-9ceaa75b5c2b44b99b756b77ef9efcbe |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T09:32:34Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9ceaa75b5c2b44b99b756b77ef9efcbe2023-11-16T17:30:52ZengMDPI AGMolecules1420-30492023-01-01283132710.3390/molecules28031327Design, Synthesis and Biological Evaluation of Conjugates of 3-<i>O</i>-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated StrainsXiaotian Lian0Wentian Liu1Bingzhi Fan2Mingjia Yu3Jianhua Liang4Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, ChinaKey Laboratory of Medical Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, ChinaKey Laboratory of Medical Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, ChinaKey Laboratory of Medical Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, ChinaKey Laboratory of Medical Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, ChinaStructurally unrelated antibiotics MLS<sub>B</sub> (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-<i>O</i>-descladinose azithromycin chemotype conjugating with nucleobases were fully explored with the aid of engineered <i>E. coli</i> 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 <i>E. coli</i> strains at the cost of lowering permeability and increasing vulnerability to efflux proteins against clinical isolates.https://www.mdpi.com/1420-3049/28/3/1327antibioticsdrug designMLS<sub>B</sub>nucleobaseSARs |
| spellingShingle | Xiaotian Lian Wentian Liu Bingzhi Fan Mingjia Yu Jianhua Liang Design, Synthesis and Biological Evaluation of Conjugates of 3-<i>O</i>-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains Molecules antibiotics drug design MLS<sub>B</sub> nucleobase SARs |
| title | Design, Synthesis and Biological Evaluation of Conjugates of 3-<i>O</i>-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains |
| title_full | Design, Synthesis and Biological Evaluation of Conjugates of 3-<i>O</i>-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains |
| title_fullStr | Design, Synthesis and Biological Evaluation of Conjugates of 3-<i>O</i>-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains |
| title_full_unstemmed | Design, Synthesis and Biological Evaluation of Conjugates of 3-<i>O</i>-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains |
| title_short | Design, Synthesis and Biological Evaluation of Conjugates of 3-<i>O</i>-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains |
| title_sort | design synthesis and biological evaluation of conjugates of 3 i o i descladinose azithromycin and nucleobases against rrna a2058g or a2059g mutated strains |
| topic | antibiotics drug design MLS<sub>B</sub> nucleobase SARs |
| url | https://www.mdpi.com/1420-3049/28/3/1327 |
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