Evaluation Of In Vitro Anti-HIV-1 And Other Pathogen Activities Of Several Sulfated Polysaccharides

AIDS is the most serious infectious disease that transmitted primarily through sex, blood and maternal-fetal. So far developing a clinically effective anti-HIV-1 vaccine has not been successful, and anti-HIV-1 drugs have widely used for AIDS therapy. However, it remains difficult to cure AIDS because of the high viral mutation and drug resistant. For control of AIDS epidemic, there is greate needs in development of alternative strategies, such as microbicides, to prevent HIV-1 from sexual transmission. Microbicides are the topical female-controled drug used in vagina before intercourse. By now, there is no any microbicide in market. As of 2006 about 62 microbicide candidates are at pre-clinical stage, 5 have entered into phase III clinical trial, 4 into phase II, more than 20 into phase I clinical trail.In order to find new microbicide candidates, we prepare sulfated polysaccharides from traditional Chinese medicine. The anti-HIV-1 activites of the polysaccharides were detected with in vitro assay, such as inhibition of syncytial formation, MTT colorimetric assay, etc. The compounds 306A, 306B, 306G, K1, F1, C1, SH1, Q4-1 and LD demonstrated a high anti-HIV-1_IIIB activity, and their 50% effective concentration (EC₅₀) were 0.10, 0.47, 0.54, 0.75, 0.23, 0.16, 0.08, 0.22, 0.21, 6.23 μg/ml, respectively, and their therapeutic index (TI) respectively were 2123, 1867, 1333, 3236, 6512, 14172, 4545, 6023. Among them, Cl has the highest anti-HIV-1_IIIB activity, and its TI was higher than that of the positive control AZT. In addition, compounds K1, 306B, SH1 and Q4-1 also showed good anti-HSV-II activity. The EC₅₀ of Kl was 85.69μg/ml, and the EC₅₀ of Q4-1, 306B and SH1 were 125.25, 167.69 and 117.07μg/ml, respectively. We did not find any obvious anti- Candida albicans activities of compounds 306A, 306G, K1, C1, SH1, Q4-1 and LD. The time-of-addition assay and pre-incubation assay showed that Q4-1 had obviously...