Investigation of σ receptors agonist/antagonist activity through N-(6-methoxytetralin-1-yl)- and N-(6-methoxynaphthalen-1-yl)alkyl derivatives of polymethylpiperidines

Bioorg Med Chem. 2013 Apr 1;21(7):1865-9. doi: 10.1016/j.bmc.2013.01.034. Epub 2013 Jan 29.

Abstract

A series of polymethyl-substituted piperidines linked to either a 6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl or a 6-methoxynaphthalen-1-yl moiety was generated with the aim of verifying a previously generated hypothesis: tetralin and naphthalene nuclei confer opposite activity at the σ1 receptor. Compounds 6, 9 and 10 displayed appreciable affinity at both σ subtypes, but none of the novel compounds displayed significant antiproliferative activity in MCF7wt and MCF7σ1 cell lines. The effect on bradikynin-triggered Ca(2+) mobilization was studied as a methodology to suggest σ receptors mediated activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Methylation
  • Naphthalenes / chemistry*
  • Naphthalenes / pharmacology*
  • Piperidines / chemistry*
  • Piperidines / pharmacology*
  • Receptors, sigma / agonists*
  • Receptors, sigma / antagonists & inhibitors*
  • Receptors, sigma / metabolism
  • Tetrahydronaphthalenes / chemistry
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Naphthalenes
  • Piperidines
  • Receptors, sigma
  • Tetrahydronaphthalenes
  • Calcium