Chemical Modification Of Porphyran From Porphyra Haitanensis And Study Of Structure-activity Relationship

Porphyra haitanensis, distributes naturally in intertidal zone of Fujian,Guangdong and Zhejiang provinces coast areas. Porphyra is not only an important economic alga, but also has been used traditionally to treat nephritic and urinary diseases etc. The basis chemical constituents in Porphyra were mainly protein, carbohydrate, vitamin and mineral. Porphyran, which was polysaccharide extracted from Porphyra is an important active composition. In the studies, we used porphyran extracted previously as raw material, modified with chemical structure and determined their bioactivities.In order to study on the relationship between chemical modification of the porphyran and their biological activity, we made the regioselective sulfated modifications on the primary and secondary hydroxyl groups and prepared the no-regioselective oversulfated derivatives. And what's more, we evaluated their antioxidant and anticoagulant activities in vitro and characterized the relationship between activities and chemical and structural characteristics. With methods of protection and removal of hydroxyl group and tactics of"One-pot Synthesis", several different derivatives were prepared. The bioactivity results indicated that fully sulfated derivatives which had high degree of substitution showed the most excellent antioxidant activities and anticoagulant activities. And sulfated derivative on the primary groups showed the better antioxidant activities than derivative on the secondary hydroxyl group, but the later showed the better anticoagulant activities than the former. And what is more, the acetylated, phosphorylated and benzoylated derivatives were prepared. The bioactivity data showed that different function groups and molecular weight took affect on the bioactivities. Among the derivatives, the benzoylated derivative showed the most remarkable antioxidant activities.The research firstly carried out fixation of 5-Fu to porphyran at 6-O through acetyl spacer group via ester bond. The chemical characteristic and release behavior of 5-FU from the conjugate obtained were studied in vitro at 37 ?C in three different medium. Analysis of release data indicated that the drug release durations of these conjugates were extremely correlated with the concentration of drug loading, the pH of media and molecular weight of the conjugates.The anticancer activities of conjugate in vitro and in vivo were also studied. For the leukemia cell HL-60, the nature porphyran showed no anticancer activity on the lower concentration, but the conjugate showed some activity. For the liver cancer cell BEL-7402, the conjugate showed better activity. At the same time, antitumor activities in vivo of conjugate were investigated. The results indicated that the conjugate showed antitumor and immunomdulation activities in different degree and could enhance antitumor activities of 5-Fu and improve immunocompetence damaged by 5-Fu.The research had important application value. As a potential anti-aging medicine, porphyran had no obvious toxic and side-effect. And it was prepared as with 5-Fu conjugate which could effectively enhance the antitumor activity of 5-Fu. Porphyran has broad prospects as a drug carrier.