Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism In Vivo. (20th February 2016)

• Record Type: Journal Article
• Authors: Dong, Ze‐Xi; Shi, Zhi‐Hao; Li, Nian‐Guang; Zhang, Wei; Gu, Ting; Zhang, Peng‐Xuan; Wu, Wen‐Yu; Tang, Yu‐Ping; Fang, Fang; Xue, Xin; Li, He‐Min; Cheng, Hai‐Bo; Yang, Jian‐Ping; Duan, Jin‐Ao
• Is Part Of: Chemical biology & drug design. Volume 87:Number 6(2016)
• Page Start: 946
• Page End: 957
• Publication Date: 2016-02-20
• Subjects: antioxidant -- scutellarein -- scutellarin -- solubility -- thrombin; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12727
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract : Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1 ) in vivo . Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1, 1‐diphenyl‐2‐picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2 O2 ‐induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c ) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2 ), which warrants further development of18c as a promising agent for ischemic cerebrovascular disease treatment. Abstract : Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1 ) in vivo . The results of the biological evaluation showed that the two isopropyl groups substituted derivative (18c ) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2 ), which warrants further development of18c as a promising agent for ischemic cerebrovascular disease treatment.