|Title||Design, synthesis, and biological evaluation of a series of bifunctional ligands of opioids/SSRIs.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Munawar MA, Lee YSun, Rankin D, Munir J, Lai J, Khan MA, Hruby VJ|
|Journal||Bioorg Med Chem|
|Date Published||2015 Mar 15|
|Keywords||Dose-Response Relationship, Drug, Drug Design, Humans, Ligands, Molecular Structure, Receptors, Opioid, Receptors, Serotonin, Serotonin Uptake Inhibitors, Structure-Activity Relationship|
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 (-12.14kcal/mol) and Ki value (1.0nM), and ΔGbind (-12.41kcal/mol) and Ki value (0.4nM), 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.
|Alternate Journal||Bioorg. Med. Chem.|
|PubMed Central ID||PMC4349363|
|Grant List||P01 DA006284 / DA / NIDA NIH HHS / United States |
R01 DA013449 / DA / NIDA NIH HHS / United States
P01DA006284 / DA / NIDA NIH HHS / United States
R01DA013449 / DA / NIDA NIH HHS / United States
Design, synthesis, and biological evaluation of a series of bifunctional ligands of opioids/SSRIs.
Faculty Member Reference:
Yeon Sun Lee, Ph.D.