Structure-Activity Relationships of Trans-Cinnamic Acid Derivatives on Α-Glucosidase Inhibition

Abstract

Trans-Cinnamic acid and its derivatives were investigated for the α-glucosidase inhibitory activity. 4-Methoxy-trans-cinnamic acid and 4-methoxy-trans-cinnamic acid ethyl ester exerted the highest potent inhibitory activity among those of trans-cinnamic acid derivatives (IC₅₀ = 0.04 ± 0.01 mM, 0.05 ± 0.03, respectively). The presence of hydroxyl or methoxy group at 4-position on trans-cinnamic acid moiety is necessary to enhance α-glucosidase inhibitory activity. However, compounds having larger alkoxy substituent were found to have little effect on α-glucosidase inhibition ( IC₅₀>5 mM).The mode of inhibition of 4-methoxy-trans-cinnamic acid on α-glucosidase activity was non-competitive with K_i value of 0.06 ± 0.01 mM. In contrast, 4-methoxy-trans-cinnamic acid ethyl ester was a competitive inhibitor with K_i value of 0.02 ± 0.01 mM. Furthermore, 4-methoxy-trans-cinnamic acid also inhibit sucrase and maltase, α-glucosidase enzymes derived from rat intestine, with IC₅₀ of 10.9 ± 0.75 mM and 8.75 ±0.80 mM, respectively. These results indicated that trans-cinnamic acid derivatives should be further evaluated as a new group of potent α-glucosidase inhibitors for the treatment of various diseases, including diabetes, anti-viral infection, and AIDS.