Title : Sugar-based multicatechol-functional biopolymers: poly[3-(3,4-Dihydroxyphenyl)glyceric acid] from medicinal plants of boraginaceae family with therapeutic efficacy
Abstract:
The main chemical constituent of high molecular (>1000 kDa) water-soluble preparations from Sym-phytum asperum, S.caucasicum, S.officinale, S.grandiflorum, Anchusa italica, Cynoglossum officinale, Paracynoglossum imeretinum and Borago officinalis (Boraginaceae) was found to be poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] that is poly[3-(3,4-dihydroxyphenyl)glyceric acid] (PDPGA) according to data of liquid-state 1H, 13C NMR, 2D 1H/13C HSQC, 2D DOSY and solid-state 13C NMR spectra. The polyoxy-ethylene chain is the backbone of this biopolymer with a residue of 3-(3,4-dihydroxyphenyl)glyceric acid as the repeating unit. 3,4-Dihydroxyphenyl (catechol) and carboxyl groups are regular substituents at two carbon atoms in the chain. Its basic monomeric moiety glyceric acid is an oxidative form of the simplest of all common aldoses glyceraldehyde. PDPGA represents a new class of natural polyethers. PDPGA as a multicatechol-functionalized poly(2,3-glyceric acid ether) belongs to a rare class of carbohydrate-based catechol-containing biopolymer as well. Poly(2,3-glyceric acid ether) chain is the backbone of this polymer and catechol groups are regular substituents at carbon atoms in the chain. Every repeating trifunctional structural unit of PDPGA con¬tains 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. PDPGA exhibited anticomplementary, antioxidant, antimicrobial, antiinflammatory, burn, wound healing and anti-cancer activities. PDPGA suppressed the growth and induced death of prostate cancer (PCA) cells. PDPGA induced apoptotic death by activating caspases, strongly decreased androgen receptor and prostate speci-fic antigen (PSA) expression. PDPGA administration caused a strong dose-dependent decrease in PSA levels by 87%. Overall, this study identifies PDPGA as a potent agent against PCA without any toxicity. Cate¬chol-containing PDPGA due to its ability to donate protons or electrons showed strong antioxidant activity. PDPGA demonstrates moderate antimicrobial properties due to the abundant catechol groups, which can denature bacterial proteins and damage bacterial cell membranes. PDPGA has also been shown to exhibit pro-oxidant activities under certain culture conditions. PDPGA due to oxidation of catechol groups into quinones can be generated various types of reactive oxygene species (ROS) such as superoxide anion (O2?•), hydrogen peroxide (H2O2), singlet oxygen (1O2), and hydroxyl radical (•OH) during oxidizing condi-tions such as autoxidation, chemical-induced oxidation, and metal ion-mediated oxidation. H2O2 is not a very potent disinfectant. The hematin (HEM), a porphyrin derivative that contains an Fe3+ ion enhance antimicrobial property of catechol. Fe3+ can convert the generated H2O2 to •OH via a Fenton-like reaction process. •OH and 1O2 are highly reactive and strong oxidant with remarkable antimicrobial properties. Be-sides, H2O2 also can be converted to more reactive oxidant such as HOCl [e.g. hypochlorite (OCl?)] by myeloperoxidase enzyme stored inside neutrophils. The resulting reactive species are the strongest anti-microbial oxidants in neutrophils. The anticomplementary activity of PDPGA is apparently related to its phenolic nature and can be explained by the formation of catechol unit – protein complexes capable of blocking complement convertases and besides inhibits xanthine oxidase and NADPH oxidase which are res-ponsible for generation of ROS. Catechol moieties of PDPGA have potent to induce production of cytoprotective proteins and consequently have a protective role against diseases, such as inflammation and cancer.
Audience Take Away:
- According to our research the novel caffeic acid-derived biopolyether poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] that is poly[3-(3,4-dihydroxyphenyl)glyceric acid] (PDPGA) was isolated and identified from medicinal plants of Boraginaceae family, which is endowed with intriguing in vitro and in vivo pharmacological properties: anticomplementary, anti-inflammatory, antimicrobial, antioxidant, burn, wound healing and anticancer, which will be important for medicinal che¬mistry and drug discovery
- The novelty of above-mentioned research the audience will be used in their job. Ether bonds are found in a wide variety of natural pro¬ducts, mainly secondary metabolites, including lipids, oxiranes, terpenoids, flavonoids, polyketides, and carbohydrate derivatives or aromatic polymer such as lignin. Lignin contains ether links between two aromatic rings or between an aromatic ring and an aliphatic moiety. However, reports concerning biopolymers that contain aliphatic ethers as repea¬ting unit were sparse
- The novelty of above-mentioned research will be used by other faculty to expand their research or teaching. Within the field of pharmacologically active biopolymers the area of stable polyethers seems ra-ther new and attractive
- The novelty of our research will be provided a practical solution to a problem that could simplify or make a designer’s job more efficient. Natural biopolymers have been gaining importance since they are already part of living beings, like proteins or polysaccharides, and thus they present higher biocompatibili-ty
- The novelty of our research will be improved the accuracy of a design, or provided new informa-tion to assist in a design problem. PDPGA is the paradigm of a multifunctional multitarget biopolyether with applications in cancer prevention and treatment
