1253696-85-3Relevant academic research and scientific papers
Synthesis of pro-prodrugs l-lysine based for 5-aminosalicylic acid and 6-mercaptopurine colon specific release
Trombino, Sonia,Cassano, Roberta,Cilea, Alessia,Ferrarelli, Teresa,Muzzalupo, Rita,Picci, Nevio
experimental part, p. 290 - 296 (2012/06/29)
The aim of this work is to design, prepare and characterize l-lysine based prodrugs capable of targeting 6-mercaptopurine to the colon, an anti-tumor and immunosuppressant drug, and 5-aminosalicylic acid (5-ASA), drug of choice for inflammatory bowel disease (IBD). More specifically, Nε-feruloyl-S-(6- purinyl)-l-lysine and Nε-acryloyl-S-(6-purinyl)-l-lysine were synthesized and then characterized by FT-IR, 1H-NMR and GC/MS spectroscopies. The ability of feruloyl derivative in inhibiting lipid peroxidation in rat liver microsomal membranes, induced in vitro by tert-butyl hydroperoxide as source of free radicals, was evaluated. Moreover, Nε-acryloyl-S-(6-purinyl)-l-lysine, polymerizable prodrug, was used to microspheres realization for 5-ASA release. These lasts, obtained by emulsion inverse technique, were characterized by light scattering and scanning electron microscopy (SEM) analysis. The microspheres equilibrium swelling degree was evaluated and showed good swelling behaviour in simulating colonic fluids. Results confirm the possibility that the application range of l-lysine prodrug can be extended to the treatment of intestinal diseases whose conventional therapy envisages medications with serious side effects that, thanks to this new strategy, can be minimized in an optimal way.
L-lysine pro-prodrug containing trans-ferulic acid for 5-amino salicylic acid colon delivery: Synthesis, characterization and in vitro antioxidant activity evaluation
Cassano, Roberta,Trombino, Sonia,Cilea, Alessia,Ferrarelli, Teresa,Muzzalupo, Rita,Picci, Nevio
body text, p. 103 - 105 (2010/05/02)
In the present work, we report the synthesis of a new 5-amino salicylic acid (5-ASA) pro-prodrug, useful in Crohn disease treatment, and the evaluation of its antioxidant activity. Using as pharmacological carrier L-lysine amino acid and taking advantage of its intrinsic chemical reactivity, due to the presence of two amino groups, placed on the chiral center and in ε-position, we inserted trans-ferulic acid in ε-position, through amidation reaction, esterified with methanol the carboxylic group and, finally, submitted the free amino group to diazotation with 5-ASA, principal drug for inflammatory bowel diseases (IBD) care. All intermediates of synthesis and the final product (derivative A) were characterized with usual spectroscopic techniques, as FT-IR, GC/MS and 1HMNR. Finally, the derivative A antioxidant activity in inhibiting the lipid peroxidation, in rat-liver microsomal membranes, induced in vitro by two different sources of free radicals, 2,2′-azobis (2-amidinopropane) (AAPH) and tert-butyl hydroperoxide (tert-BOOH), was evaluated. Our pro-prodrug could be successfully applied in pharmaceutical field both as prodrug of 5-ASA than as carrier of trans-ferulic acid.
