Document 0257
 DOCN  M9460257
 TI    Hexaprenoid hydroquinones, novel inhibitors of the reverse transcriptase
       of human immunodeficiency virus type 1.
 DT    9404
 AU    Loya S; Tal R; Hizi A; Issacs S; Kashman Y; Loya Y; Department of Cell
       Biology and Histology, Sackler School of; Medicine, Tel Aviv, Israel.
 SO    J Nat Prod. 1993 Dec;56(12):2120-5. Unique Identifier : AIDSLINE
       MED/94180131
 AB    Activity against human immunodeficiency virus type 1 (HIV-1) reverse
       transcriptase (RT) in the organic extract of the Red Sea sponge
       Toxiclona toxius was traced by us to five novel natural compounds,
       namely toxiusol [1], shaagrockol B [3], shaagrockol C [4], toxicol A
       [6], all of which are sulfated hexaprenoid hydroquinones, and toxicol B
       [7], the p-hydroquinone derivative of compound 6. The hydrolysis of the
       two sulfated compounds 1 and 4 yielded the corresponding hydroquinones
       designated as compounds 2 and 5, and further oxidation of compound 7
       afforded the corresponding p-quinone derivative, compound 8. All
       compounds exhibited inhibitory activity of both DNA polymerizing
       functions of HIV-1 RT but failed to inhibit the RT-associated
       ribonuclease H activity. Toxiusol [1] was found to be the most potent
       inhibitor of the RNA-dependent DNA polymerase function (with 50%
       inhibition obtained at 1.5 microM and 95% inhibition at 4.6 microM),
       whereas the DNA-dependent DNA polymerase was significantly less
       sensitive to the inhibitor (with 50% inhibition achieved at 6.6 microM
       and 95% inhibition only at 41.6 microM). The fact that compound 1
       discriminates between the two DNA polymerase activities of the RT offers
       new prospects for developing potent and highly specific anti-RT
       compounds, since the RNA-dependent DNA polymerase activity of RT is the
       only unique function that is not expressed at significant levels in
       uninfected mammalian cells.
 DE    Animal  Antiviral Agents/*ISOLATION & PURIF/PHARMACOLOGY  Human
       Hydroquinones/*ISOLATION & PURIF/PHARMACOLOGY  HIV-1/DRUG
       EFFECTS/*ENZYMOLOGY  Marine Toxins/*CHEMISTRY/PHARMACOLOGY
       Porifera/*CHEMISTRY  Reverse Transcriptase/*ANTAGONISTS & INHIB
       Support, U.S. Gov't, P.H.S.  Terpenes/*ISOLATION & PURIF/PHARMACOLOGY
       JOURNAL ARTICLE

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