1. Development of 6′-N-Acylated Isepamicin Analogs with Improved Antibacterial Activity against Isepamicin-Resistant Pathogens.
- Author
-
Ban, Yeon Hee, Song, Myoung Chong, Kim, Hee Jin, Lee, Heejeong, Wi, Jae Bok, Park, Je Won, Lee, Dong Gun, and Yoon, Yeo Joon
- Subjects
GRAM-negative bacteria ,PATHOGENIC microorganisms ,ACETYLTRANSFERASES ,ACYLTRANSFERASES ,ANTIBIOTICS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF