Synthesis and Biological Evaluation of Acetylcholinesterase Inhibitor Macakurzin C and Its Derivatives

Abstract

The derivatives of macakurzin C containing a modified D ring and protected C(3)/C(5)-hydroxyl groups were synthesized and their in vitro AChE inhibitory activity and neurotoxicity were evaluated to identify the structural requirements for the activities. The results indicated that C(3)-benzyl-protected derivative has a more potent AChE inhibitory activity (IC50, 2.6 μM) and a less neurotoxicity (GI50, >100 μM) than synthetic macakurzin C (IC50, 9.1 μM; GI50, 16.6 μM).

Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator

“…The synthesis of macakurzin C derivatives ( 2–7 ) was performed as previously described ( Lee et al ., 2014 ; Baek et al ., 2015 ). The effect of compound 1 and its derivatives 2–7 on adiponectin biosynthesis was evaluated during adipogenesis in hBM-MSCs ( Fig.…”

“…Macakurzin C (5,7-dihydroxy-2,2-dimethyl-8-phenyl- 2H , 6H -pyrano[3,2-g]chromen-6-one) ( 1 ), a natural flavonoid isolated from the leaves of Macaranga kurzii, was reported to have acetylcholinesterase inhibitory activity ( Trinh Thi Thanh et al ., 2012 ). Synthetic macakurzin C derivatives were shown to improve acetylcholinesterase inhibitory activity compared to that of macakurzin C ( Lee et al ., 2014 ; Baek et al ., 2015 ). In addition, synthetic macakurzin C derivatives inhibited phorbol 12-myristate 13-acetate- and oxazolone-induced dermal inflammation ( Akram et al ., 2016 ).…”

Antiviral Activity of Chrysin Derivatives against Coxsackievirus B3 in vitro and in vivo

“…Known chrysin derivatives 2–6 were prepared from chrysin (1) according to the procedure previously described in the literature (Kim et al ., 2014; Lee et al ., 2014a; Lee et al ., 2014b; Baek et al ., 2015). C(5) benzyl- and 4-substituted benzyl-protected chrysin derivatives 7–11 were prepared using conventional synthetic methods in three steps (MOM protection of chrysin, benzylation, and deprotection of MOM group) as described in Fig.…”

“…However, no studies on the anti-CVB3 activity of chrysin and its derivatives have been reported to date. Continuing our efforts towards the synthesis and biological evaluation of flavonoid-based natural products (Kim et al ., 2014; Lee et al ., 2014a; Lee et al ., 2014b; Baek et al ., 2015), we embarked on the synthesis of chrysin derivatives and studied the antiviral effect of chrysin and its derivatives against CVB3. Herein, we report the antiviral activity of chrysin-derivatives against CVB3 in vitro and in vivo .…”