Sugar based biopolymers: Poly(Sugar Acid) – Poly[3-(3,4-dihydroxyphenyl) Glyceric Acid] from medicinal plants of boraginaceae family, its synthetic analogues and therapeutic efficacy

Sugar based bio-polymers have widely used in medicine and pharmaceutics. According to data of liquid-state 1H, 13C NMR, 2D 1H/13C HSQC, 2D DOSY and solid-state 13C NMR spectra 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 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 regular polymer with a residue of 3-(3,4-dihydroxyphenyl)glyceric acid as the repeating unit. PDPGA as 3,4-dihydroxyphenyl derivative of poly(2,3-glyceric acid ether) belongs to a class of poly(sugar acids). Poly(2,3-glyceric acid ether) chain is the backbone of this polymer and 3,4-dihydroxyphenyl groups are regular substituents at carbon atoms in the chain. Repeating structural unit of PDPGA contains three reactive functional groups, two phenolic hydroxyl groups in ortho-position and one carboxyl group. Oligomers of PDPGA was synthesized by “green” chemistry enzymatic ring opening polymerization of methyl 3-(3,4-dibenzyloxyphenyl)glycidate using lipase from Candida rugosa and further deprotection. Hyaluronidase (Hyal-1) degrades high molecular mass hyaluronic acid into smaller fragments which have pro-inflammatory effects. PDPGA possesses the ability to inhibit the enzymatic activity of Hyal-1 completely. Consequently, PDPGA exhibited anti-inflammatory efficacy. PDPGA exerted anticancer activity in vitro and in vivo against prostate cancer (PCA) cells via targeting androgen receptor, cell cycle arrest and apoptosis without any toxicity, together with a strong decrease in prostate specific antigen level in plasma. Thus, PDPGA was identified as a potent agent against PCA without any toxicity.