Synthesis and biological evaluation of backbone-aminated analogues of gramicidin S.

Authors :: Rathman BM
Allen JL
Shaw LN
Del Valle JR
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Aug 01; Vol. 30 (15), pp. 127283. Date of Electronic Publication: 2020 May 22.
Publication Year :: 2020
Abstract: We report the parallel synthesis of gramicidin S derivatives featuring backbone N-amino substituents. Analogues were prepared by incorporation of N-amino dipeptide subunits on solid support. Nine backbone-aminated macrocycles were evaluated for growth inhibitory activity against ESKAPE pathogens and hemolytic activity against human red blood cells. Diamination of the Orn residues in the β-strand region of gramicidin S was found to enhance broad-spectrum antimicrobial activity without a corresponding increase in hemolytic activity.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Subjects :: Acinetobacter baumannii drug effects
Anti-Bacterial Agents chemical synthesis
Anti-Bacterial Agents chemistry
Dose-Response Relationship, Drug
Enterobacter cloacae drug effects
Enterococcus faecium drug effects
Gramicidin chemical synthesis
Gramicidin chemistry
Humans
Klebsiella pneumoniae drug effects
Microbial Sensitivity Tests
Molecular Structure
Pseudomonas aeruginosa drug effects
Staphylococcus aureus drug effects
Structure-Activity Relationship
Anti-Bacterial Agents pharmacology
Erythrocytes drug effects
Gramicidin pharmacology

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