Document 0699
 DOCN  M9440699
 TI    DNA cleavage, antiviral and cytotoxic reactions photosensitized by
       simple enediyne compounds.
 DT    9404
 AU    Kagan J; Wang X; Chen X; Lau KY; Batac IV; Tuveson RW; Hudson JB;
       Department of Chemistry, University of Illinois at Chicago; 60607-7061.
 SO    J Photochem Photobiol B. 1993 Dec;21(2-3):135-42. Unique Identifier :
       AIDSLINE MED/94132958
 AB    Very potent antibiotic antitumor natural products contain a enediyne
       moiety which, upon thermal activation, is capable of abstracting
       hydrogens from DNA. 1,6-Diphenyl-3-hexene-1,5-diyne was selected as a
       candidate for inducing DNA strand breaks photochemically. Easily
       interconverted with light, both geometric isomers 1 and 2 were expected
       to be phototoxic. As anticipated, they photosensitized the production of
       strand breaks in double-stranded supercoiled pBR322, and in
       single-stranded M13 DNA. The DNA cleavage reactions were favored by the
       presence of oxygen and were inhibited by ethanol. Preliminary
       experiments with the (Z)-isomer indicated moderate light-dependent
       antiviral activity against human immunodeficiency virus (HIV), Sindbis
       virus, and mouse cytomegalovirus. The enediynes were cytotoxic to
       Escherichia coli, a gram-negative organism, to Streptococcus faecalis, a
       gram-positive organism, to Daphnia magna and to fish (Pimephales
       promelas), but only in the presence of light. The production of
       o-terphenyl, the expected product of Bergman cyclization of 1, could not
       be confirmed. However, both 1 and 2 photosensitized the formation of
       singlet oxygen and of superoxide anion radical, and photodynamic
       reactions could have been responsible for some of the phototoxic
       reactions observed.
 DE    Alkynes/CHEMISTRY/*TOXICITY  Animal  Bacteriophage M13  Daphnia/DRUG
       EFFECTS  *DNA Damage  DNA, Viral/DRUG EFFECTS  Enterococcus
       faecalis/DRUG EFFECTS  Escherichia coli/DRUG EFFECTS  Fishes  Isomerism
       Mice  Oxygen/ANALYSIS  Photochemistry  Photosensitizing Agents/*TOXICITY
       Plasmids/DRUG EFFECTS  Spectrophotometry  Superoxides/ANALYSIS  Support,
       Non-U.S. Gov't  3T3 Cells  JOURNAL ARTICLE

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