Ito H, Shoji Y, Itabashi Y, Matsumoto K, Ohkubo K, Fukuhara K, Nakanishi I

Free Radical Research, 59 (2025)

Catechin is a major antioxidant and also shows anti-cancer effect. We have synthesized a catechin analog possessing a planar structure, planar catechin, which has 10-fold larger radical-scavenging activity than the parental (+)-catechin, and demonstrated that the planar catechin showed a significant cytotoxicity in cancer cells. However, the planar catechin has a possibility to lose the innate activity before reaching target cells, because of the higher reactivity with other biological molecules. In this study, we introduced acetyl groups to the phenolic hydroxy groups, which are considered as active sites of the planar catechin, in order to protect from the oxidation of the planar catechin, and examined the effects on cells regarding the toxicity. The acetylated planar catechin showed a remarkable cytotoxicity compared to the original planar catechin, especially in cancer cells, whereas the superoxide scavenging activity of the acetylated planar catechin was weak. On the other hand, after the acetylated planar catechin was treated with esterase, the enhanced superoxide scavenging activity was confirmed by an electron paramagnetic resonance technique. These results indicate that the activity of the planar catechin was maintained by acetylation of the phenolic hydroxy groups and the deprotection by intracellular esterase restored the activity, leading to the induction of the severe cytotoxicity.