先端化学工学ジャーナル

概要

A rare class of poly(sugar acids): Novel acidic polysaccharide 3,4-dihydroxyphenyl derivative of poly(2,3-glyceric acid ether) from medicinal plants of boraginaceae family and its anticancer efficacy

Vakhtang Barbakadze

The main chemical constit¬uent of high molecular (>1000 kDa) water-soluble preparations from medicinal plants of Symphytum asperum, S.caucasicum, S.officinale, S.grandiflorum,Anchusa italica, Cynoglossum officinale and Borago officinalis (Boraginaceae) according to data of liquid-state 1H, 13C NMR, 2D 1H/13CHSQC, 2D DOSY and solid-state 13C NMR spectra was found to be poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl) ethylene] or poly[3-(3,4-dihydroxyphenyl)-glyceric acid] (PDPGA). The polyoxyethylene chain is the backbone of this biopolymer with a residue of3-(3,4-dihydroxyphenyl)glyceric acid as the repeating unit. PDPGA as a 3,4-dihydroxyphenyl derivative of poly(2,3-glyceric acid ether) belongs to a rare class of an acidic polysaccharides [poly(sugar acids)] as well. In this case poly(2,3-glyceric acid ether) chain is the backbone of this polymer molecule and3,4-dihydroxyphenyl groups are regular substituents at 3C carbon atoms in the chain. Every repeating structural unit of a unique PDPGA contains three reactive functional groups, two phenolic hydroxyl groups in ortho-position and one carboxyl group. Multifunctionality of PDPGA should be a reason of its wide spectrum of biological activities. Oligomers of PDPGA was synthesized by “green” chemistry enzymatic ring opening polymerisation of methyl 3-(3,4-dibenzyloxyphenyl)glycidate using lipase from Candida rugosa and further deprotections. Enzymatically obtained oligomers cause interest for diverse biological tests. PDPGA exerted anticancer activity in vitro and in vivo against androgen-dependentand-independenthumanprostate cancer (PCA) cells viatargetingandrogenreceptor, cellcyclearrestandapoptosiswithoutany toxicity, togetherwitha strongdecrease (87%)inprostate specific antigen level in plasma. Thus, PDPGA was identified as a potent agent against PCA without any toxicity.