Development of 6 '-N-Acylated Isepamicin Analogs with Improved Antibacterial Activity against Isepamicin-Resistant Pathogens
- Authors
- Ban, Yeon Hee; Song, Myoung Chong; Kim, Hee Jin; Lee, Heejeong; Wi, Jae Bok; Park, Je Won; Lee, Dong Gun; Yoon, Yeo Joon
- Issue Date
- 6월-2020
- Publisher
- MDPI
- Keywords
- isepamicin analogs; 6 ' -N-acylation; enzymatic synthesis; antibacterial activity; cytotoxicity
- Citation
- BIOMOLECULES, v.10, no.6
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMOLECULES
- Volume
- 10
- Number
- 6
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/55415
- DOI
- 10.3390/biom10060893
- ISSN
- 2218-273X
- Abstract
- The development of new aminoglycoside (AG) antibiotics has been required to overcome the resistance mechanism of AG-modifying enzymes (AMEs) of AG-resistant pathogens. The AG acetyltransferase, AAC(6')-APH(2 ''), one of the most typical AMEs, exhibiting substrate promiscuity towards a variety of AGs and acyl-CoAs, was employed to enzymatically synthesize new 6'-N-acylated isepamicin (ISP) analogs, 6'-N-acetyl/-propionyl/-malonyl ISPs. They were all active against the ISP-resistant Gram-negative bacteria tested, and the 6'-N-acetyl ISP displayed reduced toxicity compared to ISP in vitro. This study demonstrated the importance of the modification of the 6'-amino group in circumventing AG-resistance and the potential of regioselective enzymatic modification of AG scaffolds for the development of more robust AG antibiotics.
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Collections - College of Health Sciences > School of Biosystems and Biomedical Sciences > 1. Journal Articles
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