Microbial Enzymatic Synthesis of Amikacin Analogs With Antibacterial Activity Against Multidrug-Resistant Pathogens

Yeon Hee Ban, Myoung Chong Song, Joong Ho Jeong, Min Seok Kwun, Chang Rae Kim, Hwi So Ryu, Eunji Kim, Je Won Park, Dong Gun Lee, Yeo Joon Yoon

Research output: Contribution to journalArticlepeer-review

Abstract

With the constant emergence of multidrug-resistant gram-negative bacteria, interest in the development of new aminoglycoside (AG) antibiotics for clinical use has increased. The regioselective modification of AG scaffolds could be an efficient approach for the development of new antibiotics with improved therapeutic potency. We enzymatically synthesized three amikacin analogs containing structural modifications in the amino groups and evaluated their antibacterial activity and cytotoxicity. Among them, 6′-N-acyl-3-N-methylated analogs showed improved antibacterial activity against the multidrug-resistant gram-negative bacteria tested, while exhibiting reduced in vitro nephrotoxicity compared to amikacin. This study demonstrated that the modifications of the 6′-amino group as well as the 3-amino group have noteworthy advantages for circumventing the AG-resistance mechanism. The regiospecific enzymatic modification could be exploited to develop novel antibacterial agents with improved pharmacological potential.

Original languageEnglish
Article number725916
JournalFrontiers in Microbiology
Volume12
DOIs
Publication statusPublished - 2021 Aug 27

Keywords

  • amikacin analogs
  • antibacterial activity
  • cytotoxicity
  • microbial enzymatic synthesis
  • multidrug-resistant pathogens

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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