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.