- Relationship between structure of conjugated oxime esters and their ability to cleave DNA
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The size and geometry of polycycles are critical to intercalation into DNA. This work involves the establishment of a new compound library that includes 35 O-benzoyl oxime esters with intercalators of five types. These conjugated compounds were synthesized by the condensation of substituted benzoyl chlorides (XC6H4COCl; X = H, Me, CN, F, and NO2) or naphthoyl chlorides with oximes of fluoren-9-one, 9,10-anthraquinone, xanthen-9-one, thioxanthen-9-one, and 9H-thioxanthen-9-one 10,10-dioxide to give the corresponding esters in 80-99% yields. All of these compounds could cleave DNA when photolyzed by UV light. Of these conjugates, 9,10-anthraquinone-O-9-(4- fluorobenzoyl)oxime with a binding constant of 4.49 × 104 M-1 cleaved DNA most efficiently. Examination of the structure-activity relationship supports a conclusion that two factors affect DNA-cleaving potency. These are (1) the planarity of the intercalating moiety, and (2) the size and substituents of the benzoyl ring. The DNA-cleaving ability followed the order 9,10-anthraquinone > fluoren-9-one ≥ xanthen-9-one ~ thioxanthen-9-one > 9H-thioxanthen-9-one 10,10-dioxide. The benzoyl-containing oxime ester conjugates were more active than the corresponding naphthoyl-containing conjugates. The potency that was associated with the different substituents on the benzoyl ring followed the order F > CN ≥ NO2 > Me ~ H.
- Hwu, Jih Ru,Tsay, Shwu-Chen,Hong, Shih Chin,Hsu, Ming-Hua,Liu, Chih-Fen,Chou, Shang-Shing P.
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p. 1778 - 1783
(2014/01/06)
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- Oxime esters of anthraquinone as photo-induced DNA-cleaving agents for single- and double-strand scissions
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Anthraquinone-O-9-(4-cyanobenzoyl)oxime (13) with binding constant of 4.49×104 M-1 exhibited single-strand scission of DNA at the concentration of 10 μM and double-strand scission at 50 μM upon UV irradiation.
- Hwu, Jih Ru,Tsay, Shwu-Chen,Hong, Shih Chin,Leu, Yi-Jing,Liu, Chih-Fen,Chou, Shang-Shing P.
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p. 2957 - 2960
(2007/10/03)
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