Investigation of Antibacterial Mode of Action for Traditional and Amphiphilic Aminoglycosides

Authors

Venkatareddy Udumula, Brigham Young University
Young Wan Ham, Brigham Young University
Marina Y. Fosso, Utah State University
Ka-Yee Chan, Utah State University
Ravi Rai, Utah State University
Jianjun Zhang, Utah State University
Jie Li, Utah State University
Cheng-Wei Tom Chang, Utah State UniversityFollow

Document Type

Article

Journal/Book Title

Bioorganic & Medicinal Chemistry Letters

Publication Date

3-15-2013

Publisher

Elsevier

Volume

23

Issue

6

First Page

1671

Last Page

1675

Abstract

Aminoglycoside represents a class of versatile and broad spectrum antibacterial agents. In an effort to revive the antibacterial activity against aminoglycoside resistant bacteria, our laboratory has developed two new classes of aminoglycoside, pyranmycin and amphiphilic neomycin (NEOF004). The former resembles the traditional aminoglycoside, neomycin. The latter, albeit derived from neomycin, appears to exert antibacterial action via a different mode of action. In order to discern that these aminoglycoside derivatives have distinct antibacterial mode of action, RNA-binding affinity and fluorogenic dye were employed. These studies, together with our previous investigation, confirm that pyranmycin exhibit the traditional antibacterial mode of action of aminoglycosides by binding toward the bacterial rRNA. On the other hand, the amphiphilic neomycin, NEOF004 disrupts the bacterial cell wall. In a broader perspective, it verifies that structurally modified neomycin can exert different antibacterial mode of action leading to the revival of activity against aminoglycoside resistant bacteria.

Comments

PubMed PMID: 23414844

Recommended Citation

Udumula, V.; Ham, Y. W.; Fosso, M. Y.; Chen, K. Y.; Rai, R.; Zhang, J.; Li, J.; Chang, C.-W. T. "Investigation of Antibacterial Mode of Action for Traditional and Amphiphilic Aminoglycosides." Bioorg. Med. Chem. Lett. 2013, 23, 1671–1675. PubMed PMID: 23414844.