Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1778-1783 |
| Number of pages | 6 |
| Journal | Bioconjugate Chemistry |
| Volume | 24 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2013 Nov 20 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Bioengineering
- Biomedical Engineering
- Pharmacology
- Pharmaceutical Science
- Organic Chemistry
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Relationship between structure of conjugated oxime esters and their ability to cleave DNA. / Hwu, Jih Ru; Tsay, Shwu Chen; Hong, Shih Chin; Hsu, Ming Hua; Liu, Chih Fen; Chou, Shang Shing P.
In: Bioconjugate Chemistry, Vol. 24, No. 11, 20.11.2013, p. 1778-1783.Research output: Contribution to journal › Article
TY - JOUR
T1 - Relationship between structure of conjugated oxime esters and their ability to cleave DNA
AU - Hwu, Jih Ru
AU - Tsay, Shwu Chen
AU - Hong, Shih Chin
AU - Hsu, Ming Hua
AU - Liu, Chih Fen
AU - Chou, Shang Shing P.
PY - 2013/11/20
Y1 - 2013/11/20
N2 - 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.
AB - 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.
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U2 - 10.1021/bc400060h
DO - 10.1021/bc400060h
M3 - Article
C2 - 24156779
AN - SCOPUS:84888583191
VL - 24
SP - 1778
EP - 1783
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 11
ER -