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

被引:46
作者
KAGAN, J
WANG, XD
CHEN, XS
LAU, KY
BATAC, IV
TUVESON, RW
HUDSON, JB
机构
[1] UNIV ILLINOIS,DEPT MICROBIOL,URBANA,IL 61810
[2] UNIV BRITISH COLUMBIA,DIV MED MICROBIOL,VANCOUVER V5Z 1M9,BC,CANADA
关键词
DAPHNIA-MAGNA; DNA CLEAVAGE; ENEDIYNES; ESCHERICHIA-COLI; HIV; MURINE CYTOMEGALOVIRUS; PBR322; DNA; PIMEPHALES-PROMELAS; PHOTOTOXICITY; SINDBIS VIRUS; STREPTOCOCCUS-FAECALIS; SINGLET OXYGEN; SUPEROXIDE;
D O I
10.1016/1011-1344(93)80175-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 tor some of the phototoxic reactions observed.
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页码:135 / 142
页数:8
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