- Synthesis of scutellarein derivatives to increase biological activity and water solubility
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In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease.
- Shi, Zhi-Hao,Li, Nian-Guang,Shi, Qian-Ping,Zhang, Wei,Dong, Ze-Xi,Tang, Yu-Ping,Zhang, Peng-Xuan,Gu, Ting,Wu, Wen-Yu,Fang, Fang,Xin-Xue,Li, He-Min,Yang, Jian-Ping,Duan, Jin-Ao
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- Efficient chemical synthesis of a scutellarein derivative containing morpholine ring
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Scutellarin (1) [5,6-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7- yl β-D-glucopyranosiduronic acid] is very effective in the clinical treatment of cerebral infarction and coronary heart disease in China. Pharmacokinetic studies showed that scutellarin (1) is readily metabolized to scutellarein (2) [5,6,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] in the intestine by β-glucuronide enzyme prior to absorption. In order to improve the biological activity of scutellarin (1), our group has previously synthesized many scutellarin derivatives based on their in vivo metabolic mechanism. The results showed that morpholine ring substituted at C-7 or C-8 position induced better antioxidant activity, water solubility and anticoagulant activity compared to scutellarin (1). In this paper, an efficient synthetic method for the construction of 5,6,7-trihydroxy-2-[4-[2-(4-morpholinyl)ethoxy] phenyl]-4H-1-benzopyran-4-one (5) is reported. This synthetic route will facilitate the synthesis of scutellarein derivatives containing an amine side chain at the C-4′ position.
- Shi, Qian-Ping,Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Hao-Tang,Zhang, Wei,Shen, Min-Zhe,Dong, Ze-Xi,Zhang, Peng-Xuan,Yang, Jian-Ping,Duan, Jin-Ao
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p. 590 - 595
(2014/07/21)
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