3--去甲氨基糖-阿奇霉素缀合物的设计、合成及针对 rRNA A2058G 或 A2059G 突变株的碱基缀合物的生物评价。
Design, Synthesis and Biological Evaluation of Conjugates of 3--Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains.
机构信息
Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China.
Yangtze Delta Region Academy, Beijing Institute of Technology, Jiaxing 314019, China.
出版信息
Molecules. 2023 Jan 30;28(3):1327. doi: 10.3390/molecules28031327.
Structurally unrelated antibiotics MLS (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--descladinose azithromycin chemotype conjugating with nucleobases were fully explored with the aid of engineered 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 strains at the cost of lowering permeability and increasing vulnerability to efflux proteins against clinical isolates.
结构上无关的抗生素 MLS（大环内酯-林可酰胺-链阳菌素 B）与临床上耐药的病原体一起受到损害，因为 rRNA A2058 的结构修饰导致了交叉耐药性。新型 3--去克拉定糖阿奇霉素化学型与核苷的结构活性关系在工程 SQ110DTC 和 SQ110LPTD 的辅助下得到了充分探索。与核碱基，特别是腺嘌呤，与克拉霉素、阿奇霉素和克林霉素相比，大环内酯类药物与核碱基的缀合物对 rRNA A2058/2059 突变的工程菌株表现出更强的抗菌优势，但其代价是降低通透性和增加对临床分离株外排蛋白的易感性。
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