DNA cleavage, antiviral and cytotoxic reactions photosensitized by simple enediyne compounds.
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.
Kagan
J
J
Department of Chemistry, University of Illinois at Chicago 60607-7061.
Wang
X
X
Chen
X
X
Lau
K Y
KY
Batac
I V
IV
Tuveson
R W
RW
Hudson
J B
JB
D016475:3T3 Cells; D000480:Alkynes / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D017104:Bacteriophage M13; D004249:DNA Damage; D004279:DNA, Viral / Q000187:drug effects; D003621:Daphnia / Q000187:drug effects; D053280:Diynes; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005399:Fishes; D007536:Isomerism; D051379:Mice; D010100:Oxygen / Q000032:analysis; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000633:toxicity*; D010957:Plasmids / Q000187:drug effects; D026082:Singlet Oxygen; D013053:Spectrophotometry; D013481:Superoxides / Q000032:analysis
D000480:Alkynes; D004279:DNA, Viral; D053280:Diynes; D017319:Photosensitizing Agents; D013481:Superoxides; D026082:Singlet Oxygen; C085658:1,6-diphenyl-3-hexene-1,5,-diyne; D010100:Oxygen