Arabinogalactan Poly- and Oligosaccharides Modified with 5-Aminosalicylic Acid

Abstract

Arabinogalactan poly-and oligosaccharides from Siberian larch (Larix sibirica L.) were modified with 5-aminosalicylic acid. The chemical composition and certain physicochemical properties were studied. The optimal conditions for preparing the modified compounds were found. These compounds were demonstrated to possess anti-ulcer and anti-inflammatory activity in tests on experimental animals.One of the methods for creating improved forms of medicinal compounds is their modification with natural polysaccharides. Among the polysaccharides that can be used for this purpose, arabinogalactan (AG) isolated by aqueous extraction from wood of the Siberian larch is of great interest because it is very soluble in water and has biological activity [1-4]. The use of water-soluble oxidized macromolecules and oligomers of AG as a polymeric matrix for formulating medicinal preparations is currently of great interest.We investigated the reaction of AG and its oxidized low-moleclar-weight fractions with an anti-ulcer preparation of 5-aminosalicylic acid (5-ASA). The low-molecular-weight fractions were prepared by oxidative destruction of AG using H 2 O 2 and atmospheric oxygen in aqueous medium. The structures of the oxidized AG fractions were previously reported [5].The modified compounds were obtained by reacting 5-ASA with AG and its oxidized fractions in water at pH 7. The synthesized compounds are light-violet to black powders that are very soluble in water but insoluble in acetone, alcohols, and ether. The natural arabinogalactan (AG na ) and polymeric (AG pol ) and oligomeric (AG ol ) fractions of oxidized polysaccharide were modified by reaction with 5-ASA, which has carboxylic, hydroxyl, and amino groups. It can be assumed that 5-ASA, like salicylic acid, is a relatively weak acid that will be partially dissociated in aqueous medium. Therefore, the form (molecular or ionized) of 5-ASA that reacts with AG must be determined. Thus, the dissociation constants of the carboxylic and hydroxyl groups of salicylic acid are K a = 1·10 -3 (pK a = 3.00) and K a = 1.5·10 -14 (pK a = 13.82), respectively [6]. Apparently these functional groups in 5-ASA are weakly dissociated. The presence of amino groups in 5-ASA typifies it also as an organic base that can accept its own protons formed by dissociation. As a result, it is obvious that the degree of dissociation of the carboxylic groups of 5-ASA should increase. Therefore, aqueous solutions of 5-ASA will contain not only acid molecules but also bipolar + H 3 NC 6 H 3 (OH)COO -ions. Dissociation of sodium salts of the acid (prepared by neutralization of an aqueous solution of the acid with base) in neutral medium will also form H 2 NC 6 H 3 (OH)COO -ions. In acid medium, + H 3 NC 6 H 3 (OH)COOH ions will most likely dominate; in basic medium, H 2 NC 6 H 3 (OH)COO -. Changing the pH of a solution is known to change the degree of dissociation of weak acids and the ratio between the concentrations of 5-ASA molecules and ions and, therefore, the UV spectra. The electronic spectrum of 5-ASA ...

Polysaccharides from Larch Biomass

“…It has been revealed that oligomeric products show anti-inflammatory and antiulcer activities. Reactions of AG and oxidized AG with some known MS give intermolecular complexes [46][47][48]. Such complexes of AG with 5-aminosalicylic acid show high antiulcer activity, while complexes incorporating 4-aminosalicylic or isonicotinic acid hydrazide demonstrate an antituberculosis effect.…”

“…Such complexes of AG with 5-aminosalicylic acid show high antiulcer activity, while complexes incorporating 4-aminosalicylic or isonicotinic acid hydrazide demonstrate an antituberculosis effect. It has been established that conjugates of AG and products of its modification increase the physiological effect of MS and decrease their toxicity [28,[46][47][48]; for instance, a conjugate of AG (9kDa) 9--Darabinofuranosyladenine-5'-monophosphate was 25-fold more active than the parent compound 9--D-arabinofuranosyladenine (araA) in decreasing the amount of hepatitis B virus, and the toxicity of the complex preparation is much lower than araA [28]. To increase reactivity of AG with MS, the synthesis of conjugates proceeds by bromination, phosphorylation, amination, formation of hydrazides or reaction with NaBH4 [27,33,34].…”