55726-29-9Relevant academic research and scientific papers
In-vitro transdermal penetration of cytarabine and its N4-alkylamide derivatives
Legoabe, Lesetja J.,Breytenbach, Jaco C.,N'Da, David D.,Breytenbach, J. Wilma
experimental part, p. 756 - 761 (2011/12/04)
Objectives: The aim of this study was to synthesise and determine the transdermal penetration of cytarabine alkylamide derivatives and assess the correlation of flux with physicochemical properties. Methods: The alkylamide derivatives of cytarabine were synthesised by acylation at the N4-amino group by the mixed anhydride method. The in-vitro permeation studies were performed using the Franz diffusion cell methodology. Furthermore, partition coefficients (n-octanol-water) and aqueous solubility of the N4-alkylamide derivatives of cytarabine were determined in order to obtain information about their lipophilicity and hydrophilicity. Key findings: The N4-alkylamides of cytarabine (acetyl, butanoyl, hexanoyl, octanoyl, and decanoyl derivatives) showed decreased hydrophilicity and increased lipophilicity. The log D values of the alkylamides were higher than that of the parent compound and increased linearly as the alkyl chain lengthened. N4-hexanoyl-4-amino-1-[(2R,3S,4R,5R)-3,4- dihydroxy-5-(hydroxymethyl)oxolan-2-yl] pyrimidin-2-one) showed the highest median steady-state flux (Jss) of 89.0 nmol/cm2 per h in the series, which shows a high statistical difference with the parent compound flux value (3.70 nmol/cm2 per h). Conclusions The prodrug approach appears to be a promising strategy for the enhancement of transdermal penetration of cytarabine.
