Synthesis and physicochemical characterization of acyl myricetins as potential anti-neuroexocytotic agents.

Acyl myricetins (monopropionyl-, dipropionyl-, and monooctanoyl-myricetin, termed as MP ₁ , MP ₂ , and MO ₁ , respectively) were synthesized through enzymatic or non-enzymatic esterification reaction of myricetin aglycone. Structure study indicated the hydroxyl group at C4' in B-ring was highly susceptible to acylation. Over its parental myricetin, acylated compounds showed enhanced lipophilicity (from 7.4- to 26.3-fold) and oxidative stability (from 1.9- to 3.1-fold) on the basis of logP and decay rate, respectively. MO ₁ , presenting the physicochemical superiority compared to the others, provided lowest EC ₅₀ value of 2.51 μM on inhibition of neutrotransmitter release and CC ₅₀ value of 59.0 μM, leading to widest therapeutic window. All myricetin esters did not show any irritation toxicity when assessed with a chicken embryo assay. This study describes information on acylation of myricetin that has not yet been explored, and suggests that MO ₁ has membrane fusion-arresting and anti-neuroexocytotic potential for industrial application due to its enhanced biological properties.
(© 2023. The Author(s).)