Modifying Heterocycles to Treat Gram + and Gram - Bacteria

Abstract

Bacterial infections are a serious threat to human health that are responsible for thousands of deaths in the United States. In order to confront this public health crisis, it is necessary to develop new interventions. A most promising treatment against pathogens will combine agents with distinct mechanism of action. This will lead to more potent therapies that can also overcome the development of bacterial resistance. Our goal for this project is to synthesize antimicrobial phenazines that can be used to modify membrane disruptors. Our hypothesis is the conjugation of the phenazines to amines, polyamines and peptides will provide systems with enhanced activity. The peptides will break the bacterial membrane allowing the penetration of the phenazine segment. We have been able to prepare and evaluate some intriguing phenazines and peptides that presented potent activity against a panel of gram positive and gram negative pathogens. We also identified some key structural features that we theorize give rise to the biological activity of the molecules.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2021
Accession Number
AD1137211

Entities

People

  • Martin Conda-Sheridan

Organizations

  • University of Nebraska Medical Center

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Health Services
  • Infection
  • Medical Personnel
  • Microbiology
  • Organic Chemistry

Readers

  • Microbial Pathology
  • Oncology
  • Systems Analysis and Design