Design, Synthesis And Antidepressant Activity Screening Of Mossol Glucoside Analogues

Depression is a highly prevalent and deleterious mental disorder whose complex neurobiology is still not well known. Many hypotheses on the etiology of depressive disorder were put forth including the monoamine hypothesis, HPA axis views, genetics and epigenetics perspectives, inflammation mechanisms, neurotrophin and neuroplasticity theories. Unmet medical needs exist in the management of depression because the response to currently-in-practice antidepressant drugs such as SSRIs and SNRIs are often inadequate and have a delayed onset of action and induce many adverse side effects. Moreover, about30percent of patients are unresponsive to the current antidepressant regimens. Thus, it is extremely necessary to discover new antidepressant drugs with novel mechanisms of action. Orcinoside is a natural product extracted from rhizoma curculiginis(a kind of Traditional Chinese Medicine), which has activities of enhancing synaptic plasticity that result in the improvement of learning and memory function when administered to laboratory animals. It is a newly discovered compound with antidepressant-like activity that may work via a distinct mechanism of action.In this thesis, orcinoside was selected as a lead and chemically modified by changing its aglycone, glycosyl group and anomeric configuration respectively. The structures of twenty one synthetic compounds were characterized by’H-NHR,13C-NMR and Mass Spectrometry.In the study, OR-A, OR-G, OR-X and orcinoside(OR-1), were evaluated for antidepressant activity by the TST and FST model. However, all of the selected compounds(20mg/kg, i.g.) did not produce antidepressant-like actions. OR-A(20mg/kg, i.g.) induced increase in the immobility time of TST, whereas had no effect on that of FST. OR-G and OR-X(20mg/kg, i.g.) resulted in a highly significant increase in the immobility time of both TST and FST, which suggested these two compounds may have the sedative effect.