Derivatives of 1,2,4-triazole imines acting as dual iNOS and tumor cell growth inhibitors

Bioorg Chem. 2020 Oct:103:104128. doi: 10.1016/j.bioorg.2020.104128. Epub 2020 Jul 22.

Abstract

A set of 4-(R2-imino)-3-mercapto-5-(R1)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.

Keywords: Anti-neoplastic agents; HT-29; HeLa; Nitric oxide synthase; Nitrofurantoin; Nitrofurazone; PAM212; PC3; Triazole; iNOS inhibitors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Growth Inhibitors / chemical synthesis
  • Growth Inhibitors / chemistry
  • Growth Inhibitors / pharmacology*
  • Imines / chemical synthesis
  • Imines / chemistry
  • Imines / pharmacology*
  • Mice
  • Molecular Structure
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / metabolism
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Growth Inhibitors
  • Imines
  • Triazoles
  • 1,2,4-triazole
  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II