ABSTRACT
In this research, phosphate and thiophosphate prodrugs 3a, 3b of anti-HIV agent AZT were synthesized, and their anti-HIV activities and cytotoxicities were investigated in vitro. Results showed that the prodrugs 3a and 3b with an IC50 value of 11.0 and 4.0 micromol x L(-1), respectively, were less toxic than AZT (1.0 micromol x L(-1)). Although the EC50 values of both 3a (0.04 micromol x (L(-1) and 3b (0.16 micromol x L(-1)) were lower than that of AZT (0.01 micromol x L(-1)), the therapeutic index (IC50/EC50) of prodrug 3a (275) was much higher than that of both AZT (100) and prodrug 3b (25). This indicated that the prodrug 3a merited further investigation as an anti-HIV agent.
Subject(s)
Humans , Anti-HIV Agents , Chemistry , Pharmacology , CD4-Positive T-Lymphocytes , Cell Biology , Cell Proliferation , Cells, Cultured , Inhibitory Concentration 50 , Prodrugs , Chemistry , Pharmacology , Zidovudine , Chemistry , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of Xianzhong Injection (XI) on morphology of knee and insulin-like growth factor-1 (IGF-1) in rabbits with early stage osteoarthritis (OA).</p><p><b>METHODS</b>One hundred and twenty rabbits were randomly divided into 5 groups, the blank group, the model group treated with 0.5 mL normal saline once a week, the positive control group treated with 0.5 mL hyaluronate once a week, and the XI 1 group and XI 2 group with 0.5 mL XI once and twice a week, respectively, all the medicines were medicated via intra-articular injection. Knee joint function was examined 8 weeks after modeling, IGF-1 content in serum and synovia was detected, and the histologic examination of articular cartilage was observed by Mallory staining as well.</p><p><b>RESULTS</b>The improvement of knee joint function was better in the XI 1 and 2 groups than that in the model group (P < 0.01), and that in the XI 1 group was equivalent to that in the positive control group (P > 0.05). Histologic examination showed there was no calcification in all the layers of cartilage in the positive control group and the XI 1 group with complete cartilaginous bluish-green collagen preserved. The content of IGF-1 increased in synovia and serum in the positive control group and the two XI groups as compared with that in the model group (P < 0.05).</p><p><b>CONCLUSION</b>XI can improve knee joint function to certain extent in early OA, and repair the degenerative cartilage.</p>