Preparation And Anti-influenza Virus Activity Of Low-molecular-weight κ-carrageenan Derivatives

Influenza is a common but difficult-to-be-controlled disease. Especially in recent years, bird-flu is spreading around the world and threatening the human health while there is a lack of corresponding drugs for both treatment and prevention. Therefore, the development of safe and effective drugs for treating and preventing influenza is a permanent and important task. The sites of action of polysaccharide drugs are often located on the surface of cells and they seldom interfere with the endocellular part, so they have low side effects. Sulfated polysaccharides show a broad-spectrum activity of anti-enveloped-virus, including influenza virus.In view of this, rapid microwave-induced depolymerization ofκ-carageenan was performed with sulfuric acid as the hydrolysis catalyst to prepare low-molecular weight (～3kDa,～5kDa,～10kD)κ-carageenan in this paper. Different acylation methods and chlorosulfonic acid-pyridine method were used to modify the low-molecular-weightκ-carageenan to improve its lipophilicity and anti-influenza activity. Finally, the invo efficacy of these low-molecular-weightκ-carageenan derivatives against influenza mouse pneumonia adaptive strain (FM1) were investigated in order to screen out one derivative which has the highest activity. The main results are listed below. The depolymerization experiments shows thatκ-carrageenan can be rapidly depolymerized to low-molecular-weight polysaccharides or oligosaccharides with a narrow molecular weight distribution using microwave as the energy source and sulfuric acid as the hydrolysis catalyst; a small increase in PH value will lead to a sharp decrease in the average molecular weight; increasing heat strength of microwave also cause decrease in the average molecular weight. IR and 13C-NMR analysis show that the acid-catalyzed depolymerization combined with microwave only destroy the glycoside bond and does not influence the repeated disaccharide.The acylation results of low-molecular-weightκ-carrageenan points out that conventional direct acylation and acylation by phase transfer catalyst (PTC, tetrabutylammonium bromide) give products with low acylation substitution degrees; comparatively, acylation using 18-crown-6 as the PTC can obtain products with much higher acylation substitution degrees and is suitable for preparing lowest-molecular-weightκ-carrageenan (～3kDa) with no larger than middle acylation substitution degrees. Ion exchange-acylation can greatly increase the acylation substitution degree, but the preparation route is too...