Design, Synthesis and Biological Evaluation of Non-Peptidic Bivalent ligands
Tanveer Ahmed, MPhil(chemistry) 2015-2017 Supervised by Dr.Mehr-un-Nisa
Design, Synthesis and Biological Evaluation of Non-Peptidic Bivalent ligands /Tanveer Ahmed - Lahore : Department of Chemistry, Div. S&T, University of Education, 2017 - 110 p. xxi CD
Selective serotonin re-uptake inhibitors (SSRIs) is a novel class of antidepressants and opioids is a class of analgesics. Opioid and SSRIs Bivalent ligands (53-60) have been designed, synthesized by direct linkage (59, 60) of two pharmacophores i.e., opioid and SSRIs and by the introduction of some spacers/linkers (53-58) between them to minimize the adverse side effect profile and checked for their opioid and SSRIs
activities for the treatment of pain and depression in a single molecule concurrently. For the design of opioids and SSRIs bivalent ligands (53-60) in Silicoand rational approaches have been applied. The synthesized bivalent ligands (53-60) have been characterized by spectroscopic analyses i.e1H NMR, 13C NMR, LRMS, HRMS. Multitarget screening of bivalent ligands (53-60) was carried out against all the brain receptors. Primary binding assay of opioid and SSRIs bivalent ligands (53-60) have
been investigated for their μ, δ and κ-opioid and SSRIs receptors. Most of the bivalent ligands 54Ki μ =o.3nM, δ =o.7nM, κ = 6nM;56Ki μ =0.6nM, δ =0.54nM, κ=0.53nM;and 58Ki μ =0.4nM, δ =0.6nM, κ =2.6nMshowed high affinities and
afficacies for μ δ and κ-opioid receptors and low affinities for SSRIs receptors. Later, functional assays of most effective ligands (53-60) have been carried out. Additional outcomes proved that these ligands (53-60) are excellent analgesics than bivalent ligands and hence could be designed in future as triple re-uptake inhibitors (TRIs) i.e., another class of antidepressants.
Biological Evaluation - Bivalent ligands - Chemistry
547.2 / D4601
Design, Synthesis and Biological Evaluation of Non-Peptidic Bivalent ligands /Tanveer Ahmed - Lahore : Department of Chemistry, Div. S&T, University of Education, 2017 - 110 p. xxi CD
Selective serotonin re-uptake inhibitors (SSRIs) is a novel class of antidepressants and opioids is a class of analgesics. Opioid and SSRIs Bivalent ligands (53-60) have been designed, synthesized by direct linkage (59, 60) of two pharmacophores i.e., opioid and SSRIs and by the introduction of some spacers/linkers (53-58) between them to minimize the adverse side effect profile and checked for their opioid and SSRIs
activities for the treatment of pain and depression in a single molecule concurrently. For the design of opioids and SSRIs bivalent ligands (53-60) in Silicoand rational approaches have been applied. The synthesized bivalent ligands (53-60) have been characterized by spectroscopic analyses i.e1H NMR, 13C NMR, LRMS, HRMS. Multitarget screening of bivalent ligands (53-60) was carried out against all the brain receptors. Primary binding assay of opioid and SSRIs bivalent ligands (53-60) have
been investigated for their μ, δ and κ-opioid and SSRIs receptors. Most of the bivalent ligands 54Ki μ =o.3nM, δ =o.7nM, κ = 6nM;56Ki μ =0.6nM, δ =0.54nM, κ=0.53nM;and 58Ki μ =0.4nM, δ =0.6nM, κ =2.6nMshowed high affinities and
afficacies for μ δ and κ-opioid receptors and low affinities for SSRIs receptors. Later, functional assays of most effective ligands (53-60) have been carried out. Additional outcomes proved that these ligands (53-60) are excellent analgesics than bivalent ligands and hence could be designed in future as triple re-uptake inhibitors (TRIs) i.e., another class of antidepressants.
Biological Evaluation - Bivalent ligands - Chemistry
547.2 / D4601
