摘要
New synthetic routes were devised for total synthesis of Fe3+-bound (ferri−) salmycin B (Sal B) (1), glycan-based Sal analogues 2–5 and their Fe3+-unbound (desferri−) counterparts 1′–5′ for the structure to activity relationship (SAR) study. The results of SAR study reveal the effective structure of 1 and its desferri-counterpart 1′ that are responsible for the observed inhibitory activity against Staphylococcus aureus (S. aureus). Among the analogues 2–5 and 2′–5′, glucose-based analogue 2 and its desferri-counterpart 2′ exhibited inhibitory potency comparable to 1 and 1′. Chemical modification of 2′ for further antibacterial study enabled us to discover desferri-Sal analogue 7′ that endowed with a simpler pharmacophore structure but significantly higher antibacterial potency against methicillin-sensitive and resistant S. aureus than the natural product 1′ and even the clinical vancomycin. Together with a better hydrolytic stability and shorter synthetic route, the analogue 7′ represents an attractive antibiotic lead for further exploration.
原文 | English |
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頁(從 - 到) | 101-113 |
頁數 | 13 |
期刊 | Advanced Synthesis and Catalysis |
卷 | 366 |
發行號 | 1 |
DOIs | |
出版狀態 | Published - 9 1月 2024 |