Chemotherapy of human immunodeficiency virus (HIV) infection: anti-HIV agents targeted at early stages in the virus replicative cycle

1996 ◽  
Vol 50 (5) ◽  
pp. 207-215 ◽  
Author(s):  
E De Clercq
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Early Stages ◽  
Immunodeficiency Virus ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Replicative Cycle

scholarly journals Potent activity of 2'-beta-fluoro-2',3'-dideoxyadenosine against human immunodeficiency virus type 1 infection in hu-PBL-SCID mice.

1996 ◽  
Vol 40 (10) ◽  
pp. 2369-2374 ◽  
Author(s):  
K Ruxrungtham ◽  
E Boone ◽  
H Ford ◽  
J S Driscoll ◽  
R T Davey ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Infection ◽  
Infection Rate ◽  
Cd4 T Cells ◽  
Scid Mice ◽  
Immunodeficiency Virus ◽  
Anti Hiv

A new antiretroviral agent, 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA), is an acid-stable compound whose triphosphate form is a potent reverse transcriptase inhibitor with in vitro anti-human immunodeficiency virus (HIV) activity and a favorable pharmacokinetic profile. Severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) provide a useful small-animal model for HIV research. In the present study we utilized this experimental system for the in vivo evaluation of the anti-HIV activity of this new compound when administered prior to infection. Initial studies revealed that, following a challenge with 50 100% tissue culture infective doses of HIV type 1 lymphadenopathy-associated virus, 39 of 42 (93%) control mice developed HIV infection, as evidenced by positive coculture or positive PCR. Administration of zidovudine decreased the infection rate to 5 of 16 (31%), while administration of FddA decreased the infection rate to 0 of 44 (0%). In follow-up controlled studies, the anti-HIV activity of FddA was confirmed, with 18 of 20 control mice showing evidence of HIV infection, compared with 4 of 20 FddA-treated mice. In addition to having direct anti-HIV effects, FddA was found to have a protective effect on human CD4+ T cells in the face of HIV infection. Mice treated with FddA were found to have a significantly higher percentage of CD4+ T cells than controls (10.3% +/- 3.4% versus 0.27% +/- 0.21%; P = 0.01). Thus, FddA, with its potent anti-HIV activity in vivo, high oral bioavailability, long intracellular half-life, and ability to preserve CD4+ cells in the presence of HIV, appears to be a promising agent for clinical investigation.

Synthesis and Antiviral Activity of 1,3-Disubstituted Uracils against HIV-1 and HCMV

2003 ◽  
Vol 14 (5) ◽  
pp. 271-279 ◽  
Author(s):  
Tokumi Maruyama ◽  
Shigetada Kozai ◽  
Tetsuo Yamasaki ◽  
Myriam Witvrouw ◽  
Christophe Pannecouque ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Human Cytomegalovirus ◽  
Therapeutic Agents ◽  
Reverse Transcriptase Inhibitors ◽  
Uracil Derivatives ◽  
Immunodeficiency Virus ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Hiv 1

The development of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) is an efficient strategy for finding new therapeutic agents against human immunodeficiency virus (HIV). A large number of 6-substituted uracil derivatives have been prepared in order to explore new NNRTIs. However, there are few approaches to anti-HIV agents from 1,3-disubstituted uracil derivatives. Therefore, we tried to prepare several 1,3-disubstituted uracils, which were easily obtainable from uracil by preparation under alkali and Mitsunobu conditions, and examined their antiviral activity against HIV-1 and human cytomegalovirus (HCMV). We found that 1-benzyl-3-(3,5-dimethylbenzyl)uracil and 1-cyanomethyl-3-(3,5-dimethylbenzyl)-4-thiouracil showed powerful inhibition against HCMV and HIV-1, respectively.

scholarly journals Synthesis and Evaluation of Some Symmetrical Phosphate Dimer Derivatives of 3′-Modified Nucleosides as Potential anti-HIV Agents

1996 ◽  
Vol 7 (6) ◽  
pp. 330-337 ◽  
Author(s):  
C. McGuigan ◽  
H.-W. Tsang ◽  
N. Mahmood ◽  
A. J. Hay
Keyword(s):  
Human Immunodeficiency Virus ◽  
Analytical Data ◽  
Modified Nucleosides ◽  
Nucleoside Analogues ◽  
Immunodeficiency Virus ◽  
Anti Hiv Agents ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Hiv 1

Novel symmetrical nucIeotide-(5′,5′)-dimers of 3′-O-acetylthymidine, 3′-O-methylthymidine, 3′-O-ethylthymidine, 3′-O-n-propylthymidine and 3′-azido-3′-deoxythymidine (AZT) were synthesized as membrane soluble pro-drugs. These were prepared using phosphorodichloridate chemistry and were characterised by spectroscopic and analytical data. In-vitro evaluation of the derivatives in cells acutely infected with the human immunodeficiency virus (HIV-1) demonstrated a range of activities. These derivatives were generally found to display poor inhibition of HIV proliferation. Derivatives containing AZT moieties were found to be potent, but such compounds were less active than the parent nucleoside. The data indicated that the AZT-containing compounds act primarily via the release of the free nucleoside. However, in some cases, the dimers of certain inactive nucleoside analogues were found to be active. In these cases, release of the nucleoside alone cannot account for the activity.

A Review on Quinoline Derived Scaffolds as Anti-HIV Agents

2019 ◽  
Vol 19 (6) ◽  
pp. 510-526 ◽  
Author(s):  
Nisha Chokkar ◽  
Sourav Kalra ◽  
Monika Chauhan ◽  
Raj Kumar
Keyword(s):  
Human Immunodeficiency Virus ◽  
Highly Active Antiretroviral Therapy ◽  
Fast Rate ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Quinolone Derivative ◽  
Immunodeficiency Syndrome ◽  
Anti Hiv Agents ◽  
Anti Hiv

After restricting the proliferation of CD4+T cells, Human Immunodeficiency Virus (HIV), infection persists at a very fast rate causing Acquired Immunodeficiency Syndrome (AIDS). This demands the vigorous need of suitable anti-HIV agents, as existing medicines do not provide a complete cure and exhibit drawbacks like toxicities, drug resistance, side-effects, etc. Even the introduction of Highly Active Antiretroviral Therapy (HAART) failed to combat HIV/AIDS completely. The major breakthrough in anti-HIV discovery was marked with the discovery of raltegravir in 2007, the first integrase (IN) inhibitor. Thereafter, the discovery of elvitegravir, a quinolone derivative emerged as the potent HIV-IN inhibitor. Though many more classes of different drugs that act as anti-HIV have been identified, some of which are under clinical trials, but the recent serious focus is still laid on quinoline and its analogues. In this review, we have covered all the quinoline-based derivatives that inhibit various targets and are potential anti-HIV agents in various phases of the drug discovery.

scholarly journals Macrophage colony-stimulating factor enhances the susceptibility of macrophages to infection by human immunodeficiency virus and reduces the activity of compounds that inhibit virus binding

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3405-3412 ◽  
Author(s):  
A Bergamini ◽  
CF Perno ◽  
L Dini ◽  
M Capozzi ◽  
CD Pesce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Dextran Sulfate ◽  
Colony Stimulating Factor ◽  
Immunodeficiency Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Anti Hiv ◽  
Stimulating Factor ◽  
Soluble Cd4

Abstract The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor expression, susceptibility to human immunodeficiency virus type 1 (HIV) infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were studied in cultured, human primary macrophages. M-CSF stimulated macrophage cells to express the CD4 receptor, and this resulted in an increase of both the number of CD4+ cells and the density of the receptor on the cell surface. M-CSF also significantly enhanced the susceptibility of macrophage cells to HIV infection. Interestingly, the anti-HIV activity of dextran sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding with different mechanisms) was reduced 100-fold and fivefold, respectively, in M-CSF- treated macrophages. Human blood concentrations of M-CSF are reported to be similar to those used in this work (1,000 U/mL); thus, it is conceivable that also in vivo this cytokine may modify the susceptibility of macrophages to HIV and the ability of dextran sulfate and soluble CD4 to inhibit HIV replication. These results suggest that the in vitro study in M-CSF-treated macrophages of promising drugs inhibitors of HIV-CD4 binding could provide further insights into the potential efficacy of these compounds in patients.

scholarly journals Macrophage colony-stimulating factor enhances the susceptibility of macrophages to infection by human immunodeficiency virus and reduces the activity of compounds that inhibit virus binding

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3405-3412 ◽  
Author(s):  
A Bergamini ◽  
CF Perno ◽  
L Dini ◽  
M Capozzi ◽  
CD Pesce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Dextran Sulfate ◽  
Colony Stimulating Factor ◽  
Immunodeficiency Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Anti Hiv ◽  
Stimulating Factor ◽  
Soluble Cd4

The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor expression, susceptibility to human immunodeficiency virus type 1 (HIV) infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were studied in cultured, human primary macrophages. M-CSF stimulated macrophage cells to express the CD4 receptor, and this resulted in an increase of both the number of CD4+ cells and the density of the receptor on the cell surface. M-CSF also significantly enhanced the susceptibility of macrophage cells to HIV infection. Interestingly, the anti-HIV activity of dextran sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding with different mechanisms) was reduced 100-fold and fivefold, respectively, in M-CSF- treated macrophages. Human blood concentrations of M-CSF are reported to be similar to those used in this work (1,000 U/mL); thus, it is conceivable that also in vivo this cytokine may modify the susceptibility of macrophages to HIV and the ability of dextran sulfate and soluble CD4 to inhibit HIV replication. These results suggest that the in vitro study in M-CSF-treated macrophages of promising drugs inhibitors of HIV-CD4 binding could provide further insights into the potential efficacy of these compounds in patients.

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