Inhibitory Effects of 3-O-Acyl-(+)-catechins on Epstein-Barr Virus Activation

Abstract

As an exploratory investigation of antitumor-promoting catechins, we tried to synthesize the (Ϫ)-epigallocatechins (EGCs) possessing an acyl group.1,2) An acyl group was introduced at the C-3 hydroxy group of (Ϫ)-EGC (2), which is less responsible for radical-scavenging action than the phenolic hydroxyl groups, 3,4) to improve their pharmacokinetic profile such as cell membrane and tissue permeability. The EGCs with the C-3 acyl chain of C 8 -C 11 carbon atoms showed marked antitumor-promoting activities both in the Epstein-Barr virus early antigen (EBV-EA) activation test and in the two-stage mouse skin carcinogenesis test were found to be especially promising candidates for cancer chemoprevention. 1,2) In the present work, we examined the inhibitory effects of 3-O-acyl derivatives of (ϩ)-catehin (1) against the activation of the EBV-EA since 1 is available at much lower price from Gambir (Asenyaku in Japanese, natural medicine, Uncaria gambir ROXB. listed in the Japanese Pharmacopoeia XIV) 5) than green tea catechins and thus could be a substitute for (Ϫ)-EGC (2) as a synthetic starting material of catechins with a 3-O-acyl group. Chemistry(ϩ)-Catechin (1) was reacted with straight-chain acid chlorides of C 4 to C 18 in tetrahydrofuran in the presence of trifluoroacetic acid.1) Preparative HPLC (GS-320 column) of the reaction mixtures gave 3-O-acyl-(ϩ)-catechins: 3, 6) 4, 5, 6, 6) 7, 8, 9, 7) and 10 in 7.7% to 16.8% yields. Furthermore, the (ϩ)-catechin derivative 11 possessing the (RS)-2-methyloctanoyl chain was synthesized by the same method as above in the expectation that it would avoid the enzyme-catalyzed hydrolytic cleavage of the ester bond in the body as in the case of the corresponding (Ϫ)-EGC derivatives. 2) Results and DisscussionThe antitumor-promoting efficacy of the synthetic 3-Oacyl-(ϩ)-catechins was estimated by measuring the inhibitory effects against the activation of EBV-EA in Raji cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The assays were performed in triplicate for each compound. No sample exhibited significant toxicity against Raji cells. As shown in Table 1, the (ϩ)-catechin derivatives 11, 5, and 6 with an acyl chain of carbon atoms C 8 -C 11 had more effect (percentage EBV-EA activationsϭ7.2, 8.8, and 10.7%, respectively) than the original (ϩ)-catechin (1) In the course of an exploratory investigation of antitumor-promoting catechins, 3-O-acyl-(؉)-catechins of varying carbon lengths from C 4 to C 18 were assessed for inhibitory effects on the activation of the Epstein-Barr virus early antigen. Like 3-O-acyl-(؊)-epigallocatechins, the (؉)-catechin derivatives showed promising effects with the C-3 acyl chain of C 8 -C 11 carbon atoms.

Anti-Staphylococcus aureus activity and oxacillin resistance modulating capacity of 3-O-acyl-catechins

“…Octanoic acid and oxacillin were purchased from Sigma (Poole, UK). The acyl-(+)-catechin derivatives and 3-O-octanoyl-(−)-epicatechin were synthesised in the Department of Biotechnology, Kansai University, Osaka, Japan as previously described [12]. Structures of the catechins used in this study are shown in Table 1.…”

Antioxidative Activity of 3-O-Octanoyl-(+)-Catechin, a Newly Synthesized Catechin, in Vitro

“…6-Hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid (Trolox) was a product of Sigma-Aldrich, Milwaukee, U.S.A. 3-O-Octanoyl-(+)-catechin was synthesized and purified as described in a previous report. 6) Other chemicals were of reagent grade. ABTS Radical Cation Decolorization Assay ---The radical scavenging activity of antioxidants for ABTS radical cations was measured according to the methods of Re et al 7) A stock solution of ABTS radical cations was prepared one day before the assay by mixing 5 ml of 7 mM ABTS with 1 ml of 14.7 mM potassium persulfate, followed by storage *To whom correspondence should be addressed: Department of Food and Nutrition, Kyoto Women's University, 35 Kitahiyoshicho, Imakumano, Higashiyama-ku, Kyoto 605-8501, Japan.…”

“…4) It has been reported that several newly synthesized 3-O-acyl-(+)-catechins, as well as 3-O-acyl-(-)-epigallocatechins, inhibited the activation of the Epstein-Barr virus early antigen more strongly than catechins lacking the 3-O-acyl group. 5,6) 3-OOctanoyl-(+)-catechin was one of the most effective derivatives. The evidence suggests that modification of 3-OH group of catechins could enhance the biological functions of the original catechins.…”

Beneficial Effects of Fragrances in Beverages on Human Health

“…Fragrant compounds should increase the sterilizing activity of liquors. Teas, especially green tea, have anti-microbial and anti-viral activities, but it is likely that these effects come from catechin derivatives such as epigallochatechin 3-O-gallate (Uesato et al, 2003).…”