title: Synthesis and Antitumor Activity of Ellagic Acid Peracetate.
abstract: Ellagic acid (1) was synthesized for the first time from methyl gallate through 3-pentagalloylglucose (α-PGG), and ellagic acid peracetate (3,4,3',4'-tetra-O-acetylellagic acid, 2) was derived from 1 by acetylation. Oral administration of 2 suppressed melanoma growth significantly in C7BL/6 immunocompetent mice without having any effect on natural killer (NK) cell activity. Comparison of the immunoenhancing activities of 1 and 2 indicated that the latter compound increased white blood cell quantities in peripheral blood and immune cells enriched from the bone marrow and liver of mice. Therefore, both the antitumor efficacy and the immunity enhancement by 2 were greater than those by 1. In addition, on oral administration neither 1 nor 2 resulted in whole body, liver, or spleen weight changes of normal, tumor-free mice, indicating that these compounds are potentially non-toxic to mice. It was shown that ellagic acid peracetate (2) inhibits B16 melanoma cell growth in vitro, and induces B16 cell apoptosis, corresponding to BCL-2 down-regulation. Collectively, the present data imply that 2 can suppress tumor growth by enhancing mouse immunity and inducing tumor cell apoptosis without apparent side effects.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Ren
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Still
authors.forename: Shunzong
authors.initials: S
authors.lastname: Yuan
authors.forename: Youcai
authors.initials: Y
authors.lastname: Deng
authors.forename: Xiaozhuo
authors.initials: X
authors.lastname: Chen
authors.forename: Klaus
authors.initials: K
authors.lastname: Himmeldirk
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu