Surprising alteration of antibacterial activity of 5″-modified neomycin against resistant bacteria

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Jianjun Zhang
  • Fang-I. Chiang
  • Long Wu
  • Przemyslaw Greg Czyryca
  • Ding Li
  • And 1 others
  • Cheng-Wei Tom Chang

Detail(s)

Original languageEnglish
Pages (from-to)7563-7573
Journal / PublicationJournal of Medicinal Chemistry
Volume51
Issue number23
Publication statusPublished - 11 Dec 2008

Abstract

A facile synthetic protocol for the production of neomycin B derivatives with various modifications at the 5″ position has been developed. The structural activity relationship (SAR) against aminoglycoside resistant bacteria equipped with various aminoglycoside-modifying enzymes (AMEs) was investigated. Enzymatic and molecular modeling studies reveal that the superb substrate promiscuity of AMEs allows the resistant bacteria to cope with diverse structural modifications despite the observation that several derivatives show enhanced antibacterial activity compared to the parent neomycin. Surprisingly, when testing synthetic neomycin derivatives against other human pathogens, two leads exhibit prominent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) that are known to exert a high level of resistance against clinically used aminoglycosides. These findings can be extremely useful in developing new aminoglycoside antibiotics against resistant bacteria. Our result also suggests that new biological and antimicrobial activities can be obtained by chemical modifications of old drugs. © 2008 American Chemical Society.

Citation Format(s)

Surprising alteration of antibacterial activity of 5″-modified neomycin against resistant bacteria. / Zhang, Jianjun; Chiang, Fang-I.; Wu, Long; Czyryca, Przemyslaw Greg; Li, Ding; Chang, Cheng-Wei Tom.

In: Journal of Medicinal Chemistry, Vol. 51, No. 23, 11.12.2008, p. 7563-7573.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal