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

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 ?-, ?- and ? opioid receptors and SSRIs receptors. Most of the compounds showed high affinities for ?- and ?-opioid receptors and lower affinities for SSRIs and ? opioid receptors. A docking study on the ?-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 ?-opioid receptor binding site with ?Gbind (-12.14kcal/mol) and Ki value (1.0nM), and ?Gbind (-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.

SUBMITTER: Mehr-un-Nisa 

PROVIDER: S-EPMC4349363 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature