Relationship Between Structure of Conjugated Oxime Esters and Their Ability to Cleave DNA

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• 作者：Jih Ru Hwu ; Shwu-Chen Tsay ; Shih Chin Hong ; Ming-Hua Hsu ; Chih-Fen Liu ; Shang-Shing P. Chou
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：November 20, 2013
• 年：2013
• 卷：24
• 期：11
• 页码：1778-1783
• 全文大小：324K
• 年卷期：v.24,no.11(November 20, 2013)
• ISSN：1520-4812

文摘

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鈥?9% 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 脳 10⁴ M^鈥? cleaved DNA most efficiently. Examination of the structure鈥揳ctivity 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 鈮?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 鈮?NO₂ > Me H.