Functionalized Ergot-alkaloids as potential dopamine D3 receptor agonists for treatment of schizophrenia

摘要: Abstract The relationship between the molecular structure and physical properties of functionalized naturally occurred Ergot -alkaloids as potential dopamine D3 receptor agonists is presented. modeling ergoline-skeleton based on comprehensive theoretical study binding affinity isolated chemicals towards active sites sub-type (D3R) loops. studied proton accepting ability under physiological conditions allows classifying four types monocationics, characterizing with different modes to D3R involving selected amino acid residues sites. These results marked pharmaceutical clinical usage reported compounds antipsychotic drugs for Schizophrenia treatment, since they allowed evaluating highlights hypothesizes biochemical causes illness. applied complex approach experimental elucidation, including quantum chemistry method, electrospray ionization (ESI) matrix assisted laser desorption/ionization (MALDI) mass spectrometric (MS) methods, nuclear magnetic resonance vibrational IR Raman spectroscopy fifteen novel derivatives ( 1 )–( 15 ) their protonated forms 1a 15a evidenced a strong dependence conformation, affinity. Thus, semi-synthetic functionalization products (NPs), provided significant possibilities further drugs-design development wanted biological function, using established profile classes/families NPs. work described chiefly non-linear (NL) interpretation chromatograms performed hybrid high performance liquid chromatography (HPLC) tandem MS/MS MS/MS/MS experiments, discussing merits great diversity instrumentation flexibility, thus achieving fundamental structural information, indispensable analysis -alkaloid derivatives, which easily converted d -lysergic (LSD).