Antidiabetic, Antidepressant, Antiparkinson’s, Neuroprotective, and Antioxidant Potentials of Novel Schiff Base Derivatives of a Lichen Metabolite, Usnic Acid

Abstract

Objective: Usnic acid, one of the most common and famous lichen acid and its Schiff base derivatives have various pharmacological activities such as analgesic, antibacterial, antiprotozoal, anti-inflammatory, anticholinergic, antiulcer, antioxidant, antiproliferative, and apoptotic properties. Dopamine, histamine and vanillylamine are the molecules that have important physiological properties in living organisms. Thus, in the current study, we aim to explore the potential pharmacological activities of novel Schiff base derivatives of usnic acid (I). Methods: Three novel Schiff base derivatives (II–IV) of usnic acid (I) were synthesized via the condensation of dopamine, histamine and vanillylamine. In vitro enzyme inhibitory effects on α-glycosidase, α-amylase, monoamine oxidases (MAO-A and MAO-B), and cholinesterase’s (AChE and BChE) and antioxidant potentials of the compounds (I–IV) were evaluated. Results and Discussion: Among the tested compounds, only ligand (II) has an antidiabetic potential inhibiting strongly both α-glycosidase and α-amylase enzymes. All of the tested molecules exhibited a remarkable antidepressant effect by inhibiting MAO-A activity; however their effects were determined to be lower than that of clorgyline. On the other hand, the antiparkinson’s and neuroprotective capabilities of (I–IV) were found to be much weaker as compared with those of pargyline and galantamine. The antioxidant potencies of (I–IV) were carried out and the compounds, (II) and (IV) acted as potent antioxidant agents by scavenging the ABTS and DPPH radicals more strongly than BHA and trolox. Conclusions: Our results point out the compound (II) is a candidate molecule for further in vitro and in vivo pharmacological studies due to its potent antidiabetic, antioxidant as well as remarkable antidepressant potentials.