Anti-HIV Activities Of Three Organic Compounds And Some Rare Earth Compounds Or Complexes

Over 21 million lives have been lost and more than 40 million people are currently living with HIV/AIDS, 3 million in 2003 alone. The intensive efforts have been undertaken to develop drugs against HIV. So far, twenty-two anti-HIV drugs were approved by FDA. Even though most pharmaceutical companies have cut the price of their products in developing countries, all anti-HIV drugs approved by FDA are still too expensive to be used for more than 90% HIV-1-infected persons living in developing countries. An effective treatment to be available to the great majority of people with HIV/AIDS is an urgent issue of global significance. In China, the number of people infected by HIV is increasing intensively, and it would severely damage the development of the country. To bring the epidemics of HIV under control, we have to develop some effective and affordable anti-HIV drugs. Here the anti-HIV activities of three organic compounds and some rare earth compounds are reported.The high titer HIV-l3B stocks were obtained from H9/HIV-l3B cultures. Viral titers were defined with 50% tissue culture infectious dose which was obtained by the measuring cytopathic effect in C8166 cells. The inhibition of HIV-lmB induced cytopathic effect was used to measure the anti-HIV activities of all agents. The cytopathic effect was assessed by counting the number of syncytia under microscope. The EC50 were further calculated according to the Reed-Muench methods. The cytotoxicities of all agents were measured by MTT colorimetric assay. This assay was based on the reduction of the MTT by mitochondrial enzymes in viable host cells to MTT formazan. The lysingsolution was added to each well. The microplate was incubated at 37 for 4 hours until sufficient color development has occurred. The blue color of the MTT formazan was then measured by microplate reader at 595/655nm. The optical density value in each well was a function of the amount of formazan produced in a number of viable cells. The CCso were calculated according to the Reed-Muench methods. Furthermore, the inhibition of PS20 on cell-cell fusion was assayed by coculturing IxlO4 chronic infected H9/HIV-lmB cells with 3*104uninfected C8166 cells. The ratio of H9/HIV-luiB cells to C8166 cells was 1:3. The cells were mixed in the presence of PS20 at serial concentrations. The time-of-addition experiments were performed to determine the steps of the replicative cycle of HIV-1 possibly inhibited by PS20. C8166 cells were infected with HIV-l,nB cultures and PS20 was added at various times point (0, 2, 4, 6, 8, 10, 24, 26h) after infection. T lymphocyte tropic HIV-1 me viral strain, C8166 and MT-4 cell lines and PBMC were used for above assays.PS20 was found to inhibit HIV-l,iiBat the EC50 of 0.19ug/ml, with TI up to 36215. The result indicated that PS20 had very strong anti-HIV-1 activity. However the anti-HIV-1 activity of P536 and C416 were demonstrated feeble. The cell-cell fusion assay showed that PS20 blocked the fusion of infected cells with uninfected cells. Time-of-addition experiment confirmed that PS20 was effective when it was added at the addition of virus. In another word, HIV replication could be inhibited when PS20 were added at the time of infection. These results suggested that PS20 interacted with the virus at the first step of HIV-1 infection. The mean of ECso and CC5o of lanthanum nitrate were 4.33ug/ml, 2664.3lug/ml respectively, its TI was 701. The result indicated that lanthanum nitrate had strong anti-HIV activity. The anti-HIV activity of cerium nitrate and lanthanum sulfate was less strong than that of lanthanum nitrate, the TIs of the two compounds were 127 and 116, respectively. The other compounds tested did not inhibit the replication of HlV-lms, and had no anti-HIV activity. The samarium, neodymium, ytterbium and platinum complexes showed very weak anti-HIV activity, the other complexes had low or no anti-HIV activity.These results demonstrated that the PS20 had high anti-HIV activity and inhibited the first step of viral infection. The anti-HIV activity of lant...