Synthesis, in silico and in vivo blood brain barrier permeability of ginkgolide B cinnamate

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• 作者：Yong-Ming Lu^a ; Jian Pan^b ; Wen-Na Zhang^a ; Ai-Ling Hui^b ; Wen-Qiang Guo^a ; Li Huang^a ; Qin-Jun Zhu^a ; Yan Chen^a ; ^{chenyan91030@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BBB ; blood brain barrier ; CNS ; central nervous system ; DTI ; drug targeting index ; GB ; ginkgolide B ; LC&ndash ; MS/MS ; liquid chromatography tandem mass spectrometry ; GBC ; ginkgolide B cinnamate
• 刊名：Fitoterapia
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：106
• 期：Complete
• 页码：110-114
• 全文大小：355 K

文摘

Ginkgolide B, one of the important components of Ginkgo biloba extracts, has been revealed to exhibit great potential in therapy of cerebrovascular diseases. However the lack of permeability greatly limited it from further clinical application. Based on the prediction model for blood brain barrier (BBB) permeation, herein a potential brain-targeting analog ginkgolide B cinnamate (GBC) was successfully synthesized and characterized. After intravenous administration of GBC or GB, liquid chromatography tandem mass spectrometry (LC–MS/MS) was conducted to determine the analog in rat plasma and brain. The results showed that GBC had a significant increase in BBB permeability. A significant 1.61-times increase in half-life was observed for GBC and the drug targeting index (DTI) value was calculated to be 9.91. The experiment results matched well with the predicted one, which revealed that BBB permeability prediction model combined with in vivo study could be used as a quick, feasible and efficient tool for brain-targeting drug design.