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
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
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
Highly active antiretroviral therapy(HAART)is used globally and has significantly reduced the morbidity,mortality,and transmission of human immunodeficiency virus(HIV)-related illness.However,the attendant shortco...Highly active antiretroviral therapy(HAART)is used globally and has significantly reduced the morbidity,mortality,and transmission of human immunodeficiency virus(HIV)-related illness.However,the attendant shortcomings such as toxic side effects,necessity of life-long therapy that is expensive, and inefficiency in eradicating latent viral infections have greatly limited the application of HAART.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
HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity a...HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity and mortality worldwide. Currently,there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects,price and drug resistance,it is essential to discover new targets,to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.展开更多
A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosam...A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1ⅢB into target cell. which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosamine were important moities to prepare gossypol derivatives as HIV- 1 entry inhibitors besides certain amino acids.展开更多
In search of potential 2',3'-dideoxyguanosine (ddG) and 2',3'-didehydro-2',3'-dideoxyguanosine (D4G) prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activi...In search of potential 2',3'-dideoxyguanosine (ddG) and 2',3'-didehydro-2',3'-dideoxyguanosine (D4G) prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cyto- toxities in cell-based assays. All analogs showed low cytotoxieities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile "one-pot" method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase (RT) incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.展开更多
Twenty-one lignans including three new ones(1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1 D and 2 D NMR analysis. Th...Twenty-one lignans including three new ones(1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1 D and 2 D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate(13) exhibited anti-HIV-1 activity with an IC50 value of 5.27 μmol·L^-1 and a selective index(SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A(3) and diphyllin(8) demonstrated inhibitory activity against HIV-1 with IC50 values of 4.95(SI > 6.2) and 0.38 μmol·L^-1(SI = 5.3), respectively.展开更多
Deamination is a crucial step in the transformation of 6-cyclopropylamino guanosine prodrug to its active form. A convenient method using capillary electrophoresis (CE) without sample labeling was developed to analy...Deamination is a crucial step in the transformation of 6-cyclopropylamino guanosine prodrug to its active form. A convenient method using capillary electrophoresis (CE) without sample labeling was developed to analyze the deamination of a series of D-/L-6-cyclopropylamino guanosine analogs by mouse liver homogenate, mouse liver microsome, and adenosine deaminase (ADA). A two-step process involving a 6-amino guanosine intermediate formed by oxidative N-dealkylation was demonstrated in the metabolism of 6-cyclopropylamino guanosine to 6-hydroxy guanosine. The results indicated that the transformation rates of different prodrugs to the active form varied greatly, which were closely correlated with the configuration of nucleosides and the structure of glycosyl groups. Most importantly, D-form analogs were metabolized much faster than their L-counterparts, thus clearly pointed out that compared to guanine, modification of glycosyl part might be a better choice for the development of L-Kuanosine analogs for the treatment of HIV,展开更多
A series of neamine-heterocycle conjugates were designed and synthesized. All new compounds displayed more potent inhibitory effect on HIV replication than neamine, among them two compounds displayed stronger anti-HIV...A series of neamine-heterocycle conjugates were designed and synthesized. All new compounds displayed more potent inhibitory effect on HIV replication than neamine, among them two compounds displayed stronger anti-HIV activity than neomycin B. The results suggested that it might be a promising approach to modify neamine for the discovery of new anti-HIV agents.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.
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.
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.
基金Youth fund of National Natural Science Foundation of China[NO.81502974]
文摘Highly active antiretroviral therapy(HAART)is used globally and has significantly reduced the morbidity,mortality,and transmission of human immunodeficiency virus(HIV)-related illness.However,the attendant shortcomings such as toxic side effects,necessity of life-long therapy that is expensive, and inefficiency in eradicating latent viral infections have greatly limited the application of HAART.
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.
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.
文摘一系列新奇 6-sulfamoyl-4-oxoquinoline-3-carboxylic 酸衍生物为 HIV integrase 抑制活动被综合了并且屏蔽。他们的结构被 ESIMS 证实, <SUP>1</SUP > H NMR 和 <SUP>13</SUP > C NMR。
文摘HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity and mortality worldwide. Currently,there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects,price and drug resistance,it is essential to discover new targets,to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.
基金the National Natural Science Foundation of China(No.30770228)for financial support
文摘A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1ⅢB into target cell. which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosamine were important moities to prepare gossypol derivatives as HIV- 1 entry inhibitors besides certain amino acids.
基金The research was supported by the fund of the National Natural Science Foundation of China,the Ministry of Science and Technology of China (No.2008ZX10303).Anti-HIV activity evaluation in pseudotyped HIV system was performed by Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College.Anti-HIV activity evaluation in HIV-1/MT2 cells was performed by HD
文摘In search of potential 2',3'-dideoxyguanosine (ddG) and 2',3'-didehydro-2',3'-dideoxyguanosine (D4G) prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cyto- toxities in cell-based assays. All analogs showed low cytotoxieities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile "one-pot" method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase (RT) incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.
基金supported by the Research Grants Council of the Hong Kong Special Administrative Region,China(Nos.HKBU12103618 and HKBU12103917)the Research Grants Council of the Hong Kong Baptist University(HKBU)+2 种基金Interdisciplinary Research Matching Scheme(No.RC-IRMS/15-16/02)the Hong Kong Scholars Program Foundation(No.XJ2015047)Mr.Kwok Yat Wai and Madam Kwok Chung Bo Fun Graduate School Development Fund(WANG Dong-Ying)
文摘Twenty-one lignans including three new ones(1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1 D and 2 D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate(13) exhibited anti-HIV-1 activity with an IC50 value of 5.27 μmol·L^-1 and a selective index(SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A(3) and diphyllin(8) demonstrated inhibitory activity against HIV-1 with IC50 values of 4.95(SI > 6.2) and 0.38 μmol·L^-1(SI = 5.3), respectively.
基金supported by National Natural Science Foundation of China (NSFC) (Nos.21172010,21002004)
文摘Deamination is a crucial step in the transformation of 6-cyclopropylamino guanosine prodrug to its active form. A convenient method using capillary electrophoresis (CE) without sample labeling was developed to analyze the deamination of a series of D-/L-6-cyclopropylamino guanosine analogs by mouse liver homogenate, mouse liver microsome, and adenosine deaminase (ADA). A two-step process involving a 6-amino guanosine intermediate formed by oxidative N-dealkylation was demonstrated in the metabolism of 6-cyclopropylamino guanosine to 6-hydroxy guanosine. The results indicated that the transformation rates of different prodrugs to the active form varied greatly, which were closely correlated with the configuration of nucleosides and the structure of glycosyl groups. Most importantly, D-form analogs were metabolized much faster than their L-counterparts, thus clearly pointed out that compared to guanine, modification of glycosyl part might be a better choice for the development of L-Kuanosine analogs for the treatment of HIV,
基金financially supported by the Ministry of Science and Technology of China(Nos.2012ZX09502001-001, 2012CB822100,and 2012CB720604)the National Natural Science Foundation of China(Nos.81025008 and 30921001)
文摘A series of neamine-heterocycle conjugates were designed and synthesized. All new compounds displayed more potent inhibitory effect on HIV replication than neamine, among them two compounds displayed stronger anti-HIV activity than neomycin B. The results suggested that it might be a promising approach to modify neamine for the discovery of new anti-HIV agents.
基金supported by the National Natural Science Fundation of China(No.30772647)the special major science and technology project of"Creation of Major New Drugs"(No.2009ZX09102-033)