Microwave assisted synthesis of naphthopyrans catalysed by silica supported fluoroboric acid as a new class of non purine xanthine oxidase inhibitors

Bioorg Med Chem Lett. 2014 Jan 15;24(2):495-500. doi: 10.1016/j.bmcl.2013.12.031. Epub 2013 Dec 16.

Abstract

A series of naphthopyrans was synthesized employing silica supported fluoroboric acid under solvent free conditions in a microwave reactor. The catalytic influence of HBF4-SiO2 was investigated in detail to optimize the reaction conditions. The synthesised compounds were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have also been presented. Among the synthesised compounds, NP-17, NP-19, NP-20, NP-23, NP-24, NP-25 and NP-26 were the active inhibitors with an IC50 ranging from 4 to 17 μM. Compound NP-19 with a thiophenyl ring at position 1 emerged as the most potent xanthine oxidase inhibitor (IC50=4 μM) in comparison to allopurinol (IC50=11.10 μM) and febuxostat (IC50=0.025 μM). The basis of significant inhibition of xanthine oxidase by NP-19 was rationalized by its molecular docking at MTE binding site of xanthine oxidase.

Keywords: Fluoroboric acid; Microwave; Naphthopyrans; Silica; Xanthine oxidase.

MeSH terms

  • Borates / chemical synthesis*
  • Borates / metabolism
  • Catalysis
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Microwaves*
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / metabolism
  • Pyrans / chemical synthesis*
  • Pyrans / metabolism
  • Silicon Dioxide / chemical synthesis*
  • Silicon Dioxide / metabolism
  • Xanthine Oxidase / antagonists & inhibitors*
  • Xanthine Oxidase / metabolism

Substances

  • Borates
  • Enzyme Inhibitors
  • Naphthalenes
  • Pyrans
  • Silicon Dioxide
  • Xanthine Oxidase
  • fluoroboric acid