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 journalArticle

4 Citations (Scopus)

Abstract

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 ΔG<inf>bind</inf> (-12.14 kcal/mol) and K<inf>i</inf> value (1.0 nM), and ΔG<inf>bind</inf> (-12.41 kcal/mol) and K<inf>i</inf> 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
Volume23
Issue number6
DOIs
StatePublished - Mar 15 2015

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Serotonin Uptake Inhibitors
Opioid Receptors
Opioid Analgesics
Serotonin
Ligands
Antidepressive Agents
Norepinephrine
Binding Sites
Depression
Pain

ASJC Scopus subject areas

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

Cite this

Design, synthesis, and biological evaluation of a series of bifunctional ligands of opioids/SSRIs. / Mehr-Un-Nisa; Munawar, Munawar A.; Lee, Yeon Sun; Rankin, David; Munir, Jawaria; Lai, Josephine; Khan, Misbahul A.; Hruby, Victor J.

In: Bioorganic and Medicinal Chemistry, Vol. 23, No. 6, 15.03.2015, p. 1251-1259.

Research output: Contribution to journalArticle

Mehr-Un-Nisa ; Munawar, Munawar A. ; Lee, Yeon Sun ; Rankin, David ; Munir, Jawaria ; Lai, Josephine ; Khan, Misbahul A. ; Hruby, Victor J. / Design, synthesis, and biological evaluation of a series of bifunctional ligands of opioids/SSRIs. In: Bioorganic and Medicinal Chemistry. 2015 ; Vol. 23, No. 6. pp. 1251-1259.
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