Design, synthesis, and biological evaluation of a series of bifunctional ligands of opioids/SSRIs

Mehr-Un-Nisa, Munawar A. Munawar, Yeon Sun Lee, David Rankin, Jawaria Munir, Josephine Lai, Misbahul A. Khan, Victor J. Hruby

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


A series of opioid and serotonin re-uptake inhibitors (SSRIs) bifunctional ligands have been designed, synthesized, and tested for their activities and efficacies at μ-, δ- and κ opioid receptors and SSRIs receptors. Most of the compounds showed high affinities for μ- and δ-opioid receptors and lower affinities for SSRIs and κ opioid receptors. A docking study on the μ-opioid receptor binding pocket has been carried out for ligands 3-11. The ligands 7 and 11 have displayed the highest binding profiles for the μ-opioid receptor binding site with ΔGbind (-12.14 kcal/mol) and Ki value (1.0 nM), and ΔGbind (-12.41 kcal/mol) and Ki value (0.4 nM), respectively. Ligand 3 was shown to have the potential of dual acting serotonin/norepinephrine re-uptake inhibitor (SNRI) antidepressant activity in addition to opioid activities, and thus could be used for the design of multifunctional ligands in the area of a novel approach for the treatment of pain and depression.

Original languageEnglish (US)
Pages (from-to)1251-1259
Number of pages9
JournalBioorganic and Medicinal Chemistry
Issue number6
StatePublished - Mar 15 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


Dive into the research topics of 'Design, synthesis, and biological evaluation of a series of bifunctional ligands of opioids/SSRIs'. Together they form a unique fingerprint.

Cite this