Document 0900
 DOCN  M9460900
 TI    New compounds related to podophyllotoxin and congeners: synthesis,
       structure elucidation and biological testing.
 DT    9404
 AU    Hansen HF; Jensen RB; Willumsen AM; Norskov-Lauritsen N; Ebbesen P;
       Nielsen PE; Buchardt O; Research Center for Medical Biotechnology, H. C.
       Orsted; Institute, University of Copenhagen, Denmark.
 SO    Acta Chem Scand. 1993 Dec;47(12):1190-200. Unique Identifier : AIDSLINE
       MED/94153633
 AB    4-Azido, 4-amino, 4-amido and 4-alkoxy compounds related to the lignans
       podophyllotoxin and 4'-demethylepipodophyllotoxin have been synthesized,
       and their structures elucidated. The Ritter reaction was shown to be
       useful in the preparation of the 4-amido compounds with the required
       stereochemistry. A preparative method for
       4-chloro-4-deoxypicrophyllotoxin, for which all earlier synthetic
       attempts resulted in the two dehydrated compounds, alpha- and
       beta-apopicropodophyllotoxin, was developed. Supplementary preliminary
       studies of the biological activities of some of the compounds were
       performed. All compounds had pronounced inhibitory effect on the in
       vitro growth of human cervical cancer cells and TC-mouse cells with
       4-amino-4-deoxypodophyllotoxin and 4-azido-4-deoxypodophyllotoxin
       showing the highest activity. Alkaline elution studies indicate that the
       toxicity of the 4'-demethoxy derivatives is due to protein-mediated DNA
       nicking. None of the compounds were found to have antiviral effect
       against herpes simplex type 2 (HSV-2), human immunodeficiency (HIV), and
       cytomegalovirus (CMV) in doses not toxic to the cells.
 DE    Animal  Antineoplastic Agents/*CHEMICAL SYNTHESIS/PHARMACOLOGY
       Antiviral Agents/*CHEMICAL SYNTHESIS/PHARMACOLOGY  Cell Line  Cell
       Survival/DRUG EFFECTS  Cervix Neoplasms/DRUG THERAPY  Colony-Forming
       Units Assay  Cytomegalovirus/DRUG EFFECTS  Female  Herpesvirus 2,
       Human/DRUG EFFECTS  Human  HIV/DRUG EFFECTS  Mice
       Podophyllotoxin/ANALOGS & DERIVATIVES/*ANALYSIS/PHARMACOLOGY  Tumor
       Cells, Cultured  JOURNAL ARTICLE

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