Each of Keggin type heteropolytungstosilicic and heteropolytungstogermanic acids reacted with 8-quinolinol, p-aminodimethylaniline and pyridine, respectively, yielding six charge trans- fer heteropolycomplexes (CTHPC...Each of Keggin type heteropolytungstosilicic and heteropolytungstogermanic acids reacted with 8-quinolinol, p-aminodimethylaniline and pyridine, respectively, yielding six charge trans- fer heteropolycomplexes (CTHPCs), which were purified and characterized by elemental analy- sis, IR, UV and 183W NMR. The anti-HIV-1 activities of CTHPCs were evaluated by ELISA of HIV-P24 antigen. The toxicity against MT-4 cells was measured by MTT. The results show that median inhibitory concentration (IC50) for each CTHPC to inhibit HIV-P24 antigen in cell culture was lower than 5 μg/mL, while median toxicity concentration (IC50) against MT-4 cells was higher than 268 μg/mL. The following mechanisms might be considered for their anti-HIV- 1 activity, namely, (1) inhibiting the penetration of HIV- 1 virus into target cells for it can blockade CD4 receptor of MT-4 cells and (2) inhibition of syncytium formation.展开更多
A series of novel 6-sulfamoyl-4-oxoquinoline-3-carboxylic acids derivatives have been synthesized and screened for HIV integrase inhibition activity. Their structures were confirmed by ESI-MS, ^1H NMR and ^13C NMR. 2...A series of novel 6-sulfamoyl-4-oxoquinoline-3-carboxylic acids derivatives have been synthesized and screened for HIV integrase inhibition activity. Their structures were confirmed by ESI-MS, ^1H NMR and ^13C NMR. 2009 Li Ming Hu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.展开更多
Anti-HIV agent (±)-calanolide A has been synthesized by a four-step approach startingfrom phloroglucinol, including the Pechmann reaction, Friedel-Crafts acylation, cyclization,chromenylation and Luche reduction.
MTT Cell Proliferation Assay was used to optimize the concentration of Telomerase Restrictors（TRs） with minimum toxicity to the selected cells. FACSort flow cytometer and Innotest P24 HIV（Human immtmodeficiency Vi...MTT Cell Proliferation Assay was used to optimize the concentration of Telomerase Restrictors（TRs） with minimum toxicity to the selected cells. FACSort flow cytometer and Innotest P24 HIV（Human immtmodeficiency Virus） antigen mAb ELISA Kit were used to investigate the anti-HIV-1 activities of TRs. The results showed that TRs had low cytotoxicity to the PBMC （Peripheral Blood mononuclear cells） and CEM/GFP if the concentration of TRs was at 50μmol/L or below, and the supernatant from PBMC pretreated with SHIV and TR1-001 /TR1-002 could not infect the PBMC, while can infect the C8166 with reduced infectivity, which suggested that the TRs may be one of the novel resources for screening anti-HIV-1 agents.展开更多
Objective To investigate the inhibitory effect of the mycelium extract from a Chinese fungus （MI） on HIV-I and its mode of action. Methods Several in vitro methods including time of action, time of addition and PCR ...Objective To investigate the inhibitory effect of the mycelium extract from a Chinese fungus （MI） on HIV-I and its mode of action. Methods Several in vitro methods including time of action, time of addition and PCR were used to test the mode of action of M 1. Results M 1 inhibited acute HIV infection in vitro and was effective when it was added 12 h after infection. PCR analysis of infected cells demonstrated that MI delayed the appearance of late product of reverse transcription and HIV was blocked before its RNA expression. Conclusion The target of M 1 is post-integration of proviral DNA.展开更多
To further explore the potential of DCK analogs as anti-HIV drug candidates, ten new tri-substituted （3＇R,4＇R）-3＇,4＇-di-O-（S）-camphanoyl-（＋）-cis-khellactone （DCK） derivatives （4-13） were designed, synth...To further explore the potential of DCK analogs as anti-HIV drug candidates, ten new tri-substituted （3＇R,4＇R）-3＇,4＇-di-O-（S）-camphanoyl-（＋）-cis-khellactone （DCK） derivatives （4-13） were designed, synthesized, and evaluated against HIV replication in MT4 cells and H9 lympho- cytes.展开更多
PLHIV have decreased economic productivity both due to direct and indirect causes. Data from developed countries have shown that at the societal level, high costs ART are offset by increased productivity. We hypothesi...PLHIV have decreased economic productivity both due to direct and indirect causes. Data from developed countries have shown that at the societal level, high costs ART are offset by increased productivity. We hypothesized that post-ART the SES would improve regardless of the baseline SES and will be sustained over time. Our objective was to perform a comprehensive SES evaluation pre/post ART initiation using an ambispective cohort study design. We used Indian household-specific SES validated tool, with score of 76 being affluent, along with clinical, ART adherence data at median of 6 and 18 months post ART, and compared using paired t-tests. Among 140 persons started on ART, with a median follow up of 22 months, 118 had Pre-ART SES data, of these: 57% were women;median age was 38 years;67% were married;89 (78%) had heterosexual sex as HIV risk;40 (34%) had major OI and/or TB at presentation. Reported self-occupation was: skilled labourers 41 (35%);12 (10%) unskilled labourers;27 (23%) housewives;26 (22%) pro-fessionals/blue collar job;1 student, 10 unemployed. The median pre-post ART CD4 cell counts were: 187 and 454 cells/cumm (P < 0.01);median body weight pre-post ART was 54 and 57 kg (P < 0.01);97% of the participants were 100% adherent. The mean Pre-ART total SES score was 37.06 (+/-10.2);and Post-ART SES score 40.62 (+10.1 P < 0.001) and these results were sustained over time and remained significant even when only monthly income was considered. Our data show a significant impact of ART on SES in a sustained manner in a developing world setting, which has policy level implications.展开更多
Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cycloph...Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.展开更多
合成了Keggin结构钨硅、钨锗、钨磷、钨砷两电子及四电子稀土钐盐杂多蓝，铈量滴定及元素分析方法确定了化合物的还原电子数及化学组成，采用 IR，UV－Vis，183 W NMR和ESR等对其结构进行了表征．在人T淋巴细胞 MT－4内，对合成的化合...合成了Keggin结构钨硅、钨锗、钨磷、钨砷两电子及四电子稀土钐盐杂多蓝，铈量滴定及元素分析方法确定了化合物的还原电子数及化学组成，采用 IR，UV－Vis，183 W NMR和ESR等对其结构进行了表征．在人T淋巴细胞 MT－4内，对合成的化合物进行了系统的抗艾滋病毒（HIV-1）活性及毒性测定．发现Keggin结构钨硅、钨锗四电子稀土钐盐杂多蓝具有较强的抗HIV-1活性，其中钨锗酸钐四电子杂多蓝（代号HPBR－2）具有较高的治疗指数．展开更多
文摘Each of Keggin type heteropolytungstosilicic and heteropolytungstogermanic acids reacted with 8-quinolinol, p-aminodimethylaniline and pyridine, respectively, yielding six charge trans- fer heteropolycomplexes (CTHPCs), which were purified and characterized by elemental analy- sis, IR, UV and 183W NMR. The anti-HIV-1 activities of CTHPCs were evaluated by ELISA of HIV-P24 antigen. The toxicity against MT-4 cells was measured by MTT. The results show that median inhibitory concentration (IC50) for each CTHPC to inhibit HIV-P24 antigen in cell culture was lower than 5 μg/mL, while median toxicity concentration (IC50) against MT-4 cells was higher than 268 μg/mL. The following mechanisms might be considered for their anti-HIV- 1 activity, namely, (1) inhibiting the penetration of HIV- 1 virus into target cells for it can blockade CD4 receptor of MT-4 cells and (2) inhibition of syncytium formation.
基金the financial supports of the National Basic Research Program(No.2009CB930200)the Fund from Beijing City Education Committee(No.KM200610005029)Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality.
文摘A series of novel 6-sulfamoyl-4-oxoquinoline-3-carboxylic acids derivatives have been synthesized and screened for HIV integrase inhibition activity. Their structures were confirmed by ESI-MS, ^1H NMR and ^13C NMR. 2009 Li Ming Hu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
文摘Anti-HIV agent (±)-calanolide A has been synthesized by a four-step approach startingfrom phloroglucinol, including the Pechmann reaction, Friedel-Crafts acylation, cyclization,chromenylation and Luche reduction.
基金Supported by China Scholarship Counsil(CSC) and Wuhan Chenguang Program of Wuhan City (2003002016-24)
文摘MTT Cell Proliferation Assay was used to optimize the concentration of Telomerase Restrictors（TRs） with minimum toxicity to the selected cells. FACSort flow cytometer and Innotest P24 HIV（Human immtmodeficiency Virus） antigen mAb ELISA Kit were used to investigate the anti-HIV-1 activities of TRs. The results showed that TRs had low cytotoxicity to the PBMC （Peripheral Blood mononuclear cells） and CEM/GFP if the concentration of TRs was at 50μmol/L or below, and the supernatant from PBMC pretreated with SHIV and TR1-001 /TR1-002 could not infect the PBMC, while can infect the C8166 with reduced infectivity, which suggested that the TRs may be one of the novel resources for screening anti-HIV-1 agents.
基金This project was supported by National Medicine Science Foundation during the 10th-five year plan period (2001BA705B01) and Chinese National Science Fund for Outstanding Youths (30325047).
文摘Objective To investigate the inhibitory effect of the mycelium extract from a Chinese fungus （MI） on HIV-I and its mode of action. Methods Several in vitro methods including time of action, time of addition and PCR were used to test the mode of action of M 1. Results M 1 inhibited acute HIV infection in vitro and was effective when it was added 12 h after infection. PCR analysis of infected cells demonstrated that MI delayed the appearance of late product of reverse transcription and HIV was blocked before its RNA expression. Conclusion The target of M 1 is post-integration of proviral DNA.
文摘To further explore the potential of DCK analogs as anti-HIV drug candidates, ten new tri-substituted （3＇R,4＇R）-3＇,4＇-di-O-（S）-camphanoyl-（＋）-cis-khellactone （DCK） derivatives （4-13） were designed, synthesized, and evaluated against HIV replication in MT4 cells and H9 lympho- cytes.
文摘PLHIV have decreased economic productivity both due to direct and indirect causes. Data from developed countries have shown that at the societal level, high costs ART are offset by increased productivity. We hypothesized that post-ART the SES would improve regardless of the baseline SES and will be sustained over time. Our objective was to perform a comprehensive SES evaluation pre/post ART initiation using an ambispective cohort study design. We used Indian household-specific SES validated tool, with score of 76 being affluent, along with clinical, ART adherence data at median of 6 and 18 months post ART, and compared using paired t-tests. Among 140 persons started on ART, with a median follow up of 22 months, 118 had Pre-ART SES data, of these: 57% were women;median age was 38 years;67% were married;89 (78%) had heterosexual sex as HIV risk;40 (34%) had major OI and/or TB at presentation. Reported self-occupation was: skilled labourers 41 (35%);12 (10%) unskilled labourers;27 (23%) housewives;26 (22%) pro-fessionals/blue collar job;1 student, 10 unemployed. The median pre-post ART CD4 cell counts were: 187 and 454 cells/cumm (P < 0.01);median body weight pre-post ART was 54 and 57 kg (P < 0.01);97% of the participants were 100% adherent. The mean Pre-ART total SES score was 37.06 (+/-10.2);and Post-ART SES score 40.62 (+10.1 P < 0.001) and these results were sustained over time and remained significant even when only monthly income was considered. Our data show a significant impact of ART on SES in a sustained manner in a developing world setting, which has policy level implications.
文摘Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.
文摘合成了Keggin结构钨硅、钨锗、钨磷、钨砷两电子及四电子稀土钐盐杂多蓝，铈量滴定及元素分析方法确定了化合物的还原电子数及化学组成，采用 IR，UV－Vis，183 W NMR和ESR等对其结构进行了表征．在人T淋巴细胞 MT－4内，对合成的化合物进行了系统的抗艾滋病毒（HIV-1）活性及毒性测定．发现Keggin结构钨硅、钨锗四电子稀土钐盐杂多蓝具有较强的抗HIV-1活性，其中钨锗酸钐四电子杂多蓝（代号HPBR－2）具有较高的治疗指数．
