A UBI 31-38 Peptide-coumarin Conjugate: Photophysical Features, Imaging Tracking and Synergism with Amphotericin B Against Cryptococcus

Curr Top Med Chem. 2018;18(2):157-163. doi: 10.2174/1568026618666180221113137.

Abstract

Cryptococcosis is a fungal disease of global significance for which new effective treatments are needed. The conjugation of the synthetic antimicrobial peptide fragment UBI 31-38 to a coumarin derivative showed to be an effective approach for the design of a novel anticryptococcal agent. In addition to antifungal activity, the conjugate exhibited intense fluorescence, which could be valuable for mechanistic investigations of this molecule. In this work, we studied the photophysical properties of the conjugate and confocal scanning laser microscopy was used to inspect the distribution of the peptide-coumarin conjugate in Cryptococcus cell. The synergism of this compound with amphotericin B or fluconazole against C. gattii and C. neoformans strains was also investigated. The results indicated that the fluorescent conjugate alone as well as its combination with amphotericin B are promising tools against cryptococcosis.

Keywords: UBI 31-38; anticryptococcal activity; confocal scanning laser microscopy; fluorescent; interaction studies; peptide-coumarin conjugate..

MeSH terms

  • Amphotericin B / chemistry
  • Amphotericin B / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Cryptococcosis / drug therapy*
  • Cryptococcus / cytology
  • Cryptococcus / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Photochemical Processes
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Coumarins
  • Peptide Fragments
  • ubiquicidin 31-38
  • Amphotericin B