1. Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism In Vivo.
- Author
-
Dong ZX, Shi ZH, Li NG, Zhang W, Gu T, Zhang PX, Wu WY, Tang YP, Fang F, Xue X, Li HM, Cheng HB, Yang JP, and Duan JA
- Subjects
- Animals, Drug Evaluation, Preclinical, PC12 Cells, Rats, Anticoagulants chemical synthesis, Anticoagulants chemistry, Anticoagulants pharmacokinetics, Anticoagulants pharmacology, Antioxidants chemical synthesis, Antioxidants chemistry, Antioxidants pharmacokinetics, Antioxidants pharmacology, Apigenin chemical synthesis, Apigenin chemistry, Apigenin pharmacokinetics, Apigenin pharmacology, Brain Ischemia drug therapy, Brain Ischemia metabolism, Drug Design, Neuroprotective Agents chemical synthesis, Neuroprotective Agents chemistry, Neuroprotective Agents pharmacokinetics, Neuroprotective Agents pharmacology
- 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 of 18c as a promising agent for ischemic cerebrovascular disease treatment., (© 2016 John Wiley & Sons A/S.)
- Published
- 2016
- Full Text
- View/download PDF