| 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 |
| Volume | 23 |
| Issue | 6 |
| Pagination | 1251-9 |
| Date Published | 2015 Mar 15 |
| ISSN | 1464-3391 |
| Keywords | Dose-Response Relationship, Drug, Drug Design, Humans, Ligands, Molecular Structure, Receptors, Opioid, Receptors, Serotonin, Serotonin Uptake Inhibitors, Structure-Activity Relationship |
| 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 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. |
| DOI | 10.1016/j.bmc.2015.01.047 |
| Alternate Journal | Bioorg. Med. Chem. |
| PubMed ID | 25703306 |
| 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 |
