Inhibition of P-glycoprotein by two artemisinin derivatives

作     者：Babette STEGLICH Anne MAHRINGER Ying LI Gary H.POSNER Gert FRICKER Thomas EFFERTH 

作者机构：Department of Pharmaceutical BiologyInstitute of Pharmacy and BiochemistryJohannes Gutenberg UniversityStaudinger Weg 5551 MainzGermany Institute of Pharmacy and Molecular BiotechnologyKarl Ruprecht UniversityHeidelbergGermany Department of Synthetic ChemistryShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina Department of ChemistryJohns Hopkins UniversityBaltimore MDUSA 

出 版 物：《Natural Products and Bioprospecting》 (应用天然产物（英文）)

年 卷 期：2012年第2卷第2期

页      面：59-64页

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 0832[工学-食品科学与工程（可授工学、农学学位）] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0901[农学-作物学] 0703[理学-化学] 100214[医学-肿瘤学] 0902[农学-园艺学] 10[医学] 

主　　题：blood brain barrier calcein multidrug resistance P-glycoprotein 

摘      要：P-Glycoprotein/MDR1 represents an important component of the blood brain barrier and contributes to multidrug *** investigated two derivatives of the anti-malarial artemisinin,SM616 and GHP-AJM-3/23,concerning their ability to interact with *** ability of the two compounds to inhibit P-glycoprotein(P-gp)activity was examined in sensitive CCRF-CEM and P-gp over-expressing and multidrug-resistant CEM/ADR5000 cells as well as in porcine brain capillary endothelial cells(PBCEC)by means of calcein-AM *** as well-known P-gp inhibitor was used as control ***/ADR5000 cells exhibited cross-resistance to GHP-AJM-3/23,but slight collateral sensitivity to ***,SM616 inhibited calcein efflux both in CEM/ADR5000 and PBCEC,whereas GHP-AJM-3/23 did only increase calcein fluorescence in PBCEC,but not CEM/*** may be explained by the fact that CEM/ADR5000 only express P-gp but not other ATP-binding cassette transporters,whereas PBCEC are known to express several ABC transporters and calcein is transported by more than one ABC ***,SM616 may be the more specific P-gp *** conclusion,the collateral sensitivity of SM616 as well as the inhibition of calcein efflux in both CEM/ADR5000 cells and PBCEC indicate that this compound may be a promising P-gp inhibitor to treat cancer therapy and to overcome the blood brain barrier.