Synthesis and Neuroprotective Activity of Novel C4, C7 Derivatives in Tetracycline Series

作     者：ZHOUZhan-yun WANGHong-tao WANGXiao-wei WNAGRui-ping DUYan-sheng LIUJun-yi ZHOU Zhan-yun;WANG Hong-tao;WANG Xiao-wei;WANG Rui-ping;DU Yan-sheng;LIU Jun-yi

作者机构：DepartmentofChemicalBiologySchoolofPharmaceueicalSciencesPekingUniversityBeijing100083China SchoolofchemicalBilolgyandPharmacyCapitalUniversityofMedicalScienecesBeijing100054China DepartmentofPharmaclolgyandToxicologyIndianaUniversitySchoolofMedicine635BarnhillDr.IndianapolisIN46202USA 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2004年第13卷第3期

页      面：217-220页

学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学] 

基　　金：NationalNaturalScienceFoundationofChina( 2 0 3 72 0 0 5 ) 

主　　题：dedimethylaminotetracycline analogs minocycline iodide neuroprotective effects reduction 

摘      要：Since the discovery of the tetracycline in 1953, numerous natural andsemisynthelic tetracyclines have been reported with broad spectrum antibacterial activity .Doxycycline 1 and minocycline 2 are semisyn-thetic second-generation tetracyclines that exertanti-inflammatory effects. These effects appear completely separate and distinct fromtheirantimicrobial actio. Minocycline and doxycycline are absorbed rapidly and show higher brainpenetrability than other tetracyclines. During recent years, doxycycline and minocycline have shownto have neuroprotective effects in models of global and focal ischemia . The neuroprotective effectsare assumed to result from the inhibition of microglia activation. Furthermore, from an in vitrostudy, it was reported that minocycline induces neuroprotection against NMDA-induced neurotoxicityby inhibiting p38 MAP ki-nase activity in microglia . However, neuroprotective mechanisms andstructure-activity relationships of these compounds in neurons are unclear.