       Document 0360
 DOCN  M9610360
 TI    Mechanistic evaluation of new plant-derived compounds that inhibit HIV-1
       reverse transcriptase.
 DT    9601
 AU    Pengsuparp T; Cai L; Constant H; Fong HH; Lin LZ; Kinghorn AD; Pezzuto
       JM; Cordell GA; Ingolfsdottir K; Wagner H; et al; Department of
       Medicinal Chemistry and Pharmacognosy, College of; Pharmacy, University
       of Illinois at Chicago 60612, USA.
 SO    J Nat Prod. 1995 Jul;58(7):1024-31. Unique Identifier : AIDSLINE
       MED/96054074
 AB    Swertifrancheside [1], a new flavonone-xanthone glucoside isolated from
       Swertia franchetiana, 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate
       [2], a triterpene isolated from the roots of Maprounea africana, and
       protolichesterinic acid [3], an aliphatic alpha-methylene-gamma-lactone
       isolated from the lichen Cetraria islandica, were found to be potent
       inhibitors of the DNA polymerase activity of human immunodeficiency
       virus-1 reverse transcriptase (HIV-1 RT), with 50% inhibitory doses
       (IC50 values) of 43, 3.7, and 24 microM, respectively. They were not
       cytotoxic with cultured mammalian cells. The kinetic mechanisms by which
       compounds 1-3 inhibited HIV-1 RT were studied as was their potential to
       inhibit other nucleic acid polymerases. Swertifrancheside [1] bound to
       DNA and was shown to be a competitive inhibitor with respect to
       template-primer, but a mixed-type competitive inhibitor with respect to
       TTP. On the other hand, 1 beta-hydroxyaleuritolic acid
       3-p-hydroxybenzoate [2] and protolichesterinic acid [3] were mixed-type
       competitive inhibitors with respect to template-primer and
       noncompetitive inhibitors with respect to TTP. Therefore, the mechanism
       of action of 1 beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate [2] and
       protolichesterinic acid [3] as HIV-1 RT inhibitors involves nonspecific
       binding to the enzyme at nonsubstrate binding sites, whereas
       swertifrancheside [1] inhibits enzyme activity by binding to the
       template-primer.
 DE    Chromatography, High Pressure Liquid  DNA/METABOLISM  DNA
       Polymerases/ANTAGONISTS & INHIB  Flavones/*PHARMACOLOGY  Human  Kinetics
       Plants, Medicinal/*CHEMISTRY  Reverse Transcriptase Inhibitors  RNA
       Polymerases/ANTAGONISTS & INHIB  Serum Albumin, Bovine/PHARMACOLOGY
       Support, U.S. Gov't, P.H.S.  Templates  Triterpenes/CHEMISTRY/*ISOLATION
       & PURIF/PHARMACOLOGY  Xanthenes/*PHARMACOLOGY  Zidovudine/PHARMACOLOGY
       4-Butyrolactone/*ANALOGS & DERIVATIVES/CHEMISTRY/ISOLATION &
       PURIF/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

