Vakhtang Barbakadze
Head of the Department of Plant Biopolymers, Tbilisi State Medical University Georgia
Title: Natural polymer of plant origin, its synthetic basic monomeric moiety and their anticancer efficacy
Biography
Biography: Vakhtang Barbakadze
Abstract
Within the field of pharmacologically active biopolymers the area of stable polyethers seems rather new and attractive. Caffeic acid-derived polyethers are a class of natural products isolated from the root extracts of comfrey and bugloss, which are endowed with intriguing pharmacological properties as anticancer agents. According to 13C, 1H NMR, APT, 2D hetero-nuclear 1H/13C HSQC, 1D NOE and 2D DOSY experiments the polyoxyethylene chain is the backbone of the polymer molecule. 3,4-Dihydroxyphenyl and carboxyl groups are regular substituents at two carbon atoms in the chain. The repeating unit of this regular polymer is 3-(3,4-dihydroxyphenyl)-glyceric acid residue. Thus, the structure of natural polymer under study was found to be poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] or poly[3-(3,4-dihydroxyphenyl)glyceric acid] (PDPGA). Then basic monomeric moiety of this polymer 3-(3,4-dihydroxyphenyl)glyceric acid was synthesized via sharpless asymmetric dihydroxylation of trans-caffeic acid derivatives using an osmium catalyst. Besides, it is well known that epoxides are valuable synthons in organic synthesis and have been introduced into several industrial, especially pharmaceutical applications, such as in the synthesis of antitumor drugs. Subsequently, the building blocks for the production of derivatives of such polyethers, methyl-3-(3,4-dimethoxyphenyl)glycidate and benzyl-3-(3,4-dibenzoxyphenyl)glycidate, were synthesized based on the Darzan reaction or by oxidation with oxone (Shi oxidation) in order to produce in future derivatives of synthetic analogue of natural polymer. PDPGA and its synthetic monomer exerted anti-cancer efficacy in vitro and in vivo against human prostate cancer (PCA) cells. Overall, this study identifies PDPGA as a potent agent against PCA without any toxicity, and supports its clinical application.