Synthesis, in silico and in vivo blood brain barrier permeability of ginkgolide B cinnamate.
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.
School of Life Sciences, Anhui University, Hefei 230601, China.
Yong-Ming
YM
Lu
Engineering Research Center of Bio-Process, Hefei University of Technology, Ministry of Education, Hefei 230009, China.
Jian
J
Pan
School of Life Sciences, Anhui University, Hefei 230601, China.
Wen-Na
WN
Zhang
Engineering Research Center of Bio-Process, Hefei University of Technology, Ministry of Education, Hefei 230009, China.
Ai-Ling
AL
Hui
School of Life Sciences, Anhui University, Hefei 230601, China.
Wen-Qiang
WQ
Guo
School of Life Sciences, Anhui University, Hefei 230601, China.
Li
L
Huang
School of Life Sciences, Anhui University, Hefei 230601, China.
Qin-Jun
QJ
Zhu
School of Life Sciences, Anhui University, Hefei 230601, China. Electronic address: chenyan91030@yahoo.com.
Yan
Y
Chen
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002853:Chromatography, Liquid; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D020441:Ginkgo biloba / Q000737:chemistry; D046934:Ginkgolides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D015394:Molecular Structure; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
D002934:Cinnamates; D046934:Ginkgolides; D007783:Lactones; C045856:ginkgolide B
Blood brain barrier; Brain-targeting; Cinnamic acid; Ginkgolide B; LC–MS; Theoretical simulation