Development of 6'-N-Acylated Isepamicin Analogs with Improved Antibacterial Activity Against Isepamicin-Resistant Pathogens.

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

SUBMITTER: Ban YH 

PROVIDER: S-EPMC7356214 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature