Modification of existing antibiotics in the form of precursor prodrugs that can be subsequently activated by nitroreductases of the target pathogen


ÇELİK A., Yetis G., AY M., GÜNGÖR T.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.26, no.16, pp.4057-4060, 2016 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 16
  • Publication Date: 2016
  • Doi Number: 10.1016/j.bmcl.2016.06.081
  • Journal Name: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.4057-4060
  • Keywords: Nitroreductase, Prodrugs, Sulfamethoxazole, ARYLAMINE N-ACETYLTRANSFERASES, LOCALIZED PROSTATE-CANCER, DRUG-METABOLISM, CLINICAL-TRIAL, THERAPY

Abstract

The use of existing antibiotics in the form of prodrug followed by activation using enzymes of pathogenic origin could be a useful approach for antimicrobial therapy. To investigate this idea, a common antibiotic, sulfamethoxazole has been redesigned in the form of a prodrug by simple functional group replacement. Upon reductive activation by a type I nitroreductase from a pathogen, the drug displayed enhanced antimicrobial capacity. This strategy could improve the efficacy and selectively of antibiotics and reduce the incidence of resistance. (C) 2016 Elsevier Ltd. All rights reserved.