Synthesis and pharmacokinetic evaluation of novel N-acyl-cordycepin derivatives with a normal alkyl chain

For slowing down the too fast metabolic velocity and increasing the bioavailability of cordycepin, four N-acyl-(propionyl-, octanoyl-, lauroyl- and stearoyl-) cordycepin derivatives were synthesized chemically and their pharmacokinetic profiles were investigated in this study. The results show that time of maximum concentration (Tmax) and half-life (t1/2) would be elongated with the increase of the alkyl chain length, but maximum concentration (Cmax) and area under concentration–time curve (AUC) increased initially, then decreased when the number of alkyl carbon exceeded eight. The Tmax, Cmax and AUC of N-octanoyl-cordycepin were nearly 4, 30 and 68 times, respectively, higher than that of cordycepin. All derivatives could be transformed into cordycepin in vivo and the concentration of transformed cordycepin was proportional to that of derivatives. It indicated that N-octanoyl modification could decrease the metabolic velocity and increase the bioavailability of cordycepin to the maximum, thus it might be a promising prodrug of cordycepin.

Graphical abstractFour novel compounds of cordycepin N-acyl derivatives with a normal alkyl chain were synthesized firstly and their pharmacokinetic and structure–activity relationship were investigated.Figure optionsDownload full-size imageDownload as PowerPoint slide