Kagan J, Wang X, Chen X, Lau K Y, Batac I V, Tuveson R W, Hudson J B
Department of Chemistry, University of Illinois at Chicago 60607-7061.
J Photochem Photobiol B. 1993 Dec;21(2-3):135-42. doi: 10.1016/1011-1344(93)80175-9.
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.
极具效力的抗生素抗肿瘤天然产物含有一个烯二炔部分，该部分在热活化时能够从DNA中夺取氢原子。1,6 - 二苯基 - 3 - 己烯 - 1,5 - 二炔被选为光化学诱导DNA链断裂的候选物。由于两种几何异构体1和2在光照下容易相互转化，预计它们都具有光毒性。正如预期的那样，它们使双链超螺旋pBR322和单链M13 DNA中产生链断裂。DNA切割反应在有氧存在时更易发生，而受到乙醇的抑制。对（Z） - 异构体的初步实验表明，其对人类免疫缺陷病毒（HIV）、辛德毕斯病毒和小鼠巨细胞病毒具有适度的光依赖性抗病毒活性。烯二炔类化合物对革兰氏阴性菌大肠杆菌、革兰氏阳性菌粪肠球菌、大型溞和鱼类（黑头软口鲦）具有细胞毒性，但仅在光照存在时才表现出毒性。无法证实1经伯格曼环化反应预期生成的邻三联苯的产生。然而，1和2都能使单线态氧和超氧阴离子自由基形成光敏化，光动力反应可能是观察到的一些光毒性反应的原因。
