Structure–activity relationship of dihydroxy-4-methylcoumarins as powerful antioxidants: Correlation between experimental & theoretical data and synergistic effect
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- 作者：Vessela D. Kancheva ; Luciano Saso ; Petya V. Boranova ; Abdullah Khan ; Manju K. Saroj ; Mukesh K. P ; ey ; Shashwat Malhotra ; Jordan Z. Nechev ; Sunil K. Sharma ; Ashok K. Prasad ; Maya B. Georgieva ; Carleta J
- 关键词：Dihydroxy-4-methylcoumarins ; Antioxidants ; Structure– ; activity relationship ; Lipinski’ ; s rule of five ; Synergistic effect
- 刊名：Biochimie
- 出版年：2010
- 出版时间：September 2010
- 年：2010
- 卷：92
- 期：9
- 页码：1089-1100
- 全文大小：736 K
文摘
The chain-breaking antioxidant activities of eight coumarins [7-hydroxy-4-methylcoumarin (1), 5,7-dihydroxy-4-methylcoumarin (2), 6,7-dihydroxy-4-methylcoumarin (3), 6,7-dihydroxycoumarin (4), 7,8-dihydroxy-4-methylcoumarin (5), ethyl 2-(7,8-dihydroxy-4-methylcoumar-3-yl)-acetate (6), 7,8-diacetoxy-4-methylcoumarin (7) and ethyl 2-(7,8-diacetoxy-4-methylcoumar-3-yl)-acetate (8)] during bulk lipid autoxidation at 37 °C and 80 °C in concentrations of 0.01–1.0 mM and their radical scavenging activities at 25 °C using TLC–DPPH test have been studied and compared. It has been found that the o-dihydroxycoumarins 3–6 demonstrated excellent activity as antioxidants and radical scavengers, much better than the m-dihydroxy analogue 2 and the monohydroxycoumarin 1. The substitution at the C-3 position did not have any effect either on the chain-breaking antioxidant activity or on the radical scavenging activity of the 7,8-dihydroxy- and 7,8-diacetoxy-4-methylcoumarins 6 and 8. The comparison with DL-α-tocopherol (TOH), caffeic acid (CA) and p-coumaric acid (p-CumA) showed that antioxidant efficiency decreases in the following sequence:
TOH > CA > 3 > 4 > 6 > 5 > 2 > 1 = 7 = 8 = p-CumA.
Theoretical calculations and the “Lipinski’s Rule of Five” were used for explaining the structure–activity relationships and pharmacokinetic behavior. A higher TGSO oxidation stability was observed in the presence of equimolar (1:1) binary mixtures of coumarins with TOH (1 + TOH, 3 + TOH and 5 + TOH). However, the synergism (14 % ) was observed only for the binary mixture of 5 + TOH.