Cyclosophoraoses (Cys) are synthesized by all members of the family Rhizobiaceae. Cys are a class of unbranched cyclic oligosaccharides composed glucose residues linked solely by β-1,2-glycosidic bonds, and the predominant ring size distribution is between 17 and 25 glucose residues. The biological activity of Cys has been studied in the peas, clovers, and beans (Phaseolus vulgaris L.) root-nodule bacteria Rhizobium leguminosarum bv. phaseoli. These molecules have been shown to provide two independent functions; namely, they are involved in the formation of nitrogen-fixing root nodules and promote the osmoadaptation of bacterial cells. Recent reports have shown that Cys forms inclusion complexes with a variety of hydrophobic guest molecules such as amphotericin B, fluorescein, flurbipropen, indomethacin, paclitaxel and vitamins. Much attention has thus been focused on their potential ability to form inclusion complexes with other lipophilic molecules as well as on their biological functions. To further applications of Cys, the cyclic oligosaccharides were modified with various functional groups such as carboxymethyl, sulfonyl, and succinyl groups. However, no attempts have yet been made a polymerization or oligomerization of Cys to improve the inclusion complexation ability. Similarly, cyclodextrins (cyclic β-1,4-glycans)based polymers are of interest due to their merits compared to parent CDs, such as high solubility in water and capability to solubilize a number of drugs, those with large molecular structures in particular. CD polymers can also increase the drug bioavailability. Therefore, the synthesized Cys polymers or oligomers would be used as efficient hosts for the solubility enhancement of hardly soluble drugs as well as for the bioavailability increase of natural compounds. Ibuprofen and naproxen are non-steroidal anti-inflammatory (NSAID), analgesic and antipyretic agent having main mechanism of action through block a group of enzymes called COX (cyclo-oxygenase) enzymes. They reduce pain as analgesic drugs, high temperatures as antipyrexial drugs, and swelling as anti-inflammatory drugs and make the blood less likely to clot as antithrombolic drugs. However, they have a very low solubility in water and when administered orally, it causes gastrointestinal side-effects, drowsiness and dizziness. Therefore, improvement of their solubility is challenging and rational. In the study, Cys were isolated from Rhizobium phaseoli, which is a member of the family Rhizobiaceae by ethanol precipitation and purified by various chromatographic techniques. An oligomeric cyclosophoraoses (oligo-Cys) were synthesized from cyclosophoraose (Cys), epichlorohydrin (EP) and choline chloride (CC) through a one-step polymerization procedure. The physicochemical properties of the modified oligo-Cys were characterized using various techniques including MALDI-TOF MS and H NMR spectroscopic analysis and the effects of the degree of Cys oligomerization on their drug inclusion performance was investigated by ultraviolet (UV)-visible spectroscopy. The formation of their inclusion complexes also was confirmed by fourier transform infrared spectroscopy (FT-IR). Preparation of water soluble oligo-Cys was achieved by the reaction of Cys, isolated and purified from Rhizobium phaseoli, with EP and CC in an alkaline medium by a one step procedure (Scheme 1). The reaction mixture was separated by Bio-Gel P-6 depends on degree of oligomerization. Fractionation of the reaction mixture on a gel filtration column of Bio-Gel P-6 yielded three major carbohydrate peaks (Fig. 1). In the MALDI-TOF MS spectra, the ring sizes of the Cys, which ranged from 17 to 24, were confirmed by MALDI-TOF MS spectrometry (Fig. 2(a)). Based on the MALDI-TOF mass spectrometric analysis, the average molecular weight (Mn) of Cys was determined as 3078 Da.
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