DNA CLEAVAGE, ANTIVIRAL AND CYTOTOXIC REACTIONS PHOTOSENSITIZED BY SIMPLE ENEDIYNE COMPOUNDS

Very potent antibiotic antitumor natural products contain a enediyne m oiety which, upon thermal activation, is capable of abstracting hydrog ens from DNA. 1,6-Diphenyl-3-hexene-1,5-diyne was selected as a candid ate for inducing DNA strand breaks photochemically. Easily interconver ted with light, both geometric isomers 1 and 2 were expected to be pho totoxic. 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 ox ygen and were inhibited by ethanol. Preliminary experiments with the ( Z)-isomer indicated moderate light-dependent antiviral activity agains t human immunodeficiency virus (HIV), Sindbis virus, and mouse cytomeg alovirus. The enediynes were cytotoxic to Escherichia coli, a gram-neg ative organism, to Streptococcus faecalis, a gram-positive organism, t o Daphnia magna and to fish (Pimephales promelas), but only in the pre sence 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 a nion radical, and photodynamic reactions could have been responsible t or some of the phototoxic reactions observed.