HIV-1 protease inhibitors play a very important role in AIDS chemotherapy, but with the rapid emergence of drug resistance as a result of the residue mutation of HIV-1 protease, developing effective protease inhibitors with superior activity against drug-resistant variants is becoming the research hotspot in AIDS drug design. Meanwhile, some molecular designing strategies of anti-drug-resistant HIV-1 protease inhibitors were put forward and applied to develop anti-AIDS drugs. The purpose of the research is introducing these molecular designing strategies to develop potent HIV-1 protease inhibitors to combat drug resistance, including substrate envelope hypothesis, strengthening the binding of inhibitors to HIV-1 protease and searching inhibitors acting in novel sites of HIV-1 protease.

This study is to investigate the antitumor activity of CIP-36 on multidrug resistant human oral squamous carcinoma cell line (KBV200 cells) in vitro and the possible anticancer mechanisms. MTT assay, Hoechst fluorescein stain, RT-PCR and immunohistochemistry were carried out on KBV200 and KB cells. The growth of many tumor cells was obviously inhibited by CIP-36, especially the multidrug resistant cells KBV200. Obvious apoptosis could be observed in the Hoechst 33342 staining experiments. The results of RT-PCR showed that the levels of p53, p21, caspase-3 and bax mRNA increased, and meanwhile the expression of mdr-1 and bcl-2 mRNA decreased in a dose-dependent manner. The data were significantly different from that of vehicle. The expression of P-gp significantly decreased with the increasing dosage of CIP-36 examined by immunohistochemistry. It can be concluded that CIP-36 could change resistance-related genes and proteins to overcome multidrug resistance in the KBV200 cell line.

Objective To study the effects of dammarane sapogenins ( DS-1226 ) on sleep interruption-induced learning and memory impairment in mice.Methods 130 SPF healthy 5 -6-week old male ICR mice were randomly divided into control, model, DS-1226 low dose, DS-1226 medium dose and DS-1226 high dose groups.The behavioral alterations in open field (OF), Morris water maze (MWM) and step-through (ST) tests were detected at 15 days after rotating drum-induced sleep interruption ( SI) .Results The total distance, movement speed, total duration of movement were increased in OF test ( P<0.05, vs.the model group) after treatment.The latency of place navigation was increased from day 5 in the MWM test after 15 d sleep interruption, and the number of crossing in the target quadrant and the percent distance in target quadrant were decreased after 15 d sleep interruption ( P <0.05, vs.the control group), while the latency of place navigation was decreased, and the percent distance in target quadrant and percent time in target quadrant after high dose DS-1226 oral administration ( P<0.05, vs.the model group) were increased.Error times, distance in dark chamber, time in dark chamber and immobility time in dark chamber were increased in training of step through test ( P<0.05, vs.the control group);while these indexes were decreased after DS-1226 oral administration ( P<0.05, vs.the model group) .But there was no significant difference in the step through testing course.Conclusions The results show that orally administrated DS-1226 can ameliorate SI-induced learning and memory impairment, and there is a significant dosage-effect relationship.

Objective The aim of this experiment was to study the improving effects of a ginsenoside hydrolysis product DS-1227 on scopolamine-induced learning and memory impairment in mice.Methods Sixty healthy 5-6-week old male ICR mice (body weight 22 ±2 g) were randomly divided into control group, model group, three DS-1227 groups (25 mg/kg, 50 mg/kg, 100 mg/kg), and positive control group (0.3 mg/kg).Fourteen days after oral administration of DS-1227, an open-field test was conduct to determine the mouse locomotor activity.Fifteen days after oral administration of DS-1227, all experimental animals were intraperitoneally administered scopolamine (0.75 mg/kg) and the mice of control group received the same volume of saline.In addition to scopolamine, the mice of positive control group received intraperitoneal injection of physostigmine in a dose of 0.3 mg/kg.Twenty minutes after completion of all the drug administration, object recognition test and Morris water maze test were conducted to evaluate the learning and memory abilities of the mice.Results DS-1227 had no significant effect on locomotor activity of the mice.Scopolamine obviously decreased the discrimination indexes in object recognition test, and prolonged the escape latency of water maze place navigation test.While 25 mg/kg, 50 mg/kg, 100 mg/kg of DS-1227 increased the discrimination indexes and decreased the escape latency of place navigation in the mice.Conclusion DS-1227 can improve the learning and memory impairment induced by scopolamine in mice.