Oltipraz, a novel inhibitor of human immunodeficiency virus type 1 (HIV‐1) replication Journal Article
| Authors: | Prochaska, H. J.; Chavan, S. J.; Baron, P.; Polsky, B. |
| Article Title: | Oltipraz, a novel inhibitor of human immunodeficiency virus type 1 (HIV‐1) replication |
| Abstract: | Glutathione (GSH) levels are markedly depleted in patients infected with human immunodeficiency virus type 1 (HIV‐1) and supplementation of media with high concentrations (5–20 mM) of low‐molecular weight thiols prevents HIV‐1 replication in cultured cells. We were intrigued whether chemo‐preventive enzyme inducers might represent a more pharmacologically feasible method to inhibit HIV‐1 replication since these compounds elevate intracellular concentrations of GSH at nontoxic doses in vivo. After establishing that all inducers surveyed were able to elevate GSH levels in human T‐cell and monocytoid cell lines, we were surprised to find that olitpraz (5‐pyrazinyl‐4‐methyl‐1,2‐dithiole‐3‐thione) was uniquely able to inhibit HIV‐1 replication (IC50 = 5–15 μM). Oltipraz and other antiviral 1,2‐dithiole‐3‐thiones (DTTs) appear to inhibit acute HIV‐1 replication by inactivating reverse transcriptase (RT). However, among DTTs that inhibit HIV‐1 replication in acutely infected cells, only oltipraz was able to inhibit HIV‐1 replication in a chronic infection model. Thus, in addition to inactivating RT, oltipraz appears to have an additional antiviral mechanism distal to viral integration. Our laboratories are attempting to determine the mechanism by which oltipraz inhibits HIV‐1 replication in chronically infected cells; we are also attempting to determine the bioorganic mechanism for the inactivation of RT. Since the covalent modification of schistosomal protein and transcription factor(s) are thought to be responsible for the antiparasitic and chemopreventive activities of DTTs, respectively, our studies should be relevant to understanding the diverse medicinal properties of DTTs. Oltipraz, an antischistosomal drug undergoing clinical evaluation as an anticarcinogen, inhibits HIV‐1 replication at concentrations achievable in human serum. It is intriguing to consider oltipraz as a therapeutic agent not only for its antiretroviral activity, but also for the prevention of HIV‐1 associated neoplasms. Copyright © 1995 Wiley‐Liss, Inc. |
| Keywords: | human cell; clinical trial; review; nonhuman; conference paper; human immunodeficiency virus infection; t lymphocyte; animal cell; mouse; pyrazines; drug effect; physiology; lymphoma cell; enzyme inactivation; antivirus agent; acquired immune deficiency syndrome; acquired immunodeficiency syndrome; virus replication; monocyte; pyrazine derivative; clinical trials; glutathione; antiviral activity; human immunodeficiency virus 1; acute disease; hiv-1; antiviral agents; chemoprevention; virus inhibition; aids; acetylcysteine; schistosomiasis; hepatoma cell; antiviral; fumaric acid dimethyl ester; rna directed dna polymerase; humans; human; priority journal; reverse transcriptase; oltipraz; antischistosomal agent; dithiolethiones; anticarcinogen; 1,2 dithiole 3 thione derivative; schistosomicides |
| Journal Title: | Journal of Cellular Biochemistry |
| Volume: | 59 |
| Issue: | Suppl. 22 |
| ISSN: | 0730-2312 |
| Publisher: | John Wiley & Sons |
| Date Published: | 1995-01-01 |
| Start Page: | 117 |
| End Page: | 125 |
| Language: | English |
| DOI: | 10.1002/jcb.240590815 |
| PUBMED: | 8538188 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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