Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives

Bioorg Med Chem. 2017 Aug 15;25(16):4375-4383. doi: 10.1016/j.bmc.2017.06.026. Epub 2017 Jun 15.

Abstract

The 7-benzylidenenaltrexone (BNTX) derivatives 2a-v, 3a-c, 13a-c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC50=10.5µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The morphinan skeleton bearing both the double bond for a Michael acceptor and the phenolic hydroxy group would be a specific template for development of antitrichomonal agents. In addition, the mechanism of the antitrichomonal activity of the BNTX derivatives may differ from that of the standard drug, metronidazole.

Keywords: Antitrichomonal activity; BNTX; Morphinan; Opioid receptor; Trichomonas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitrichomonal Agents / chemical synthesis
  • Antitrichomonal Agents / chemistry
  • Antitrichomonal Agents / pharmacology*
  • Benzylidene Compounds / chemical synthesis
  • Benzylidene Compounds / chemistry
  • Benzylidene Compounds / pharmacology*
  • CHO Cells
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Naltrexone / analogs & derivatives*
  • Naltrexone / chemical synthesis
  • Naltrexone / chemistry
  • Naltrexone / pharmacology
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Trichomonas vaginalis / drug effects*

Substances

  • Antitrichomonal Agents
  • Benzylidene Compounds
  • Receptors, Opioid, delta
  • 7-benzylidenenaltrexone
  • Naltrexone