Identifying urotropine derivatives as co-donors of formaldehyde and nitric oxide for improving antitumor therapy

Chem Commun (Camb). 2021 Aug 7;57(61):7581-7584. doi: 10.1039/d1cc02177j. Epub 2021 Jul 12.

Abstract

A pharmacophore integration strategy was utilized to develop the first co-donor of formaldehyde and nitric oxide (FANO), composed of urotropine derived nitramine/nitrosamine. FANO simultaneously generated formaldehyde and nitric oxide on-demand, resulting in synergistic anticancer effects. Importantly, liposomal formulation of FANO effectively inhibited tumor growth with minimal side-effects, providing a potent combined nitric oxide therapy for malignancy.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Carriers / chemistry
  • Formaldehyde / metabolism*
  • Liposomes / chemistry
  • Methenamine / chemistry
  • Mice
  • Neoplasms / drug therapy*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / chemical synthesis
  • Nitric Oxide Donors / therapeutic use*
  • Nitrosamines / chemical synthesis
  • Nitrosamines / therapeutic use
  • Polyamines / chemical synthesis
  • Polyamines / therapeutic use*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • Nitric Oxide Donors
  • Nitrosamines
  • Polyamines
  • Formaldehyde
  • Nitric Oxide
  • Methenamine