title: Synthesis of pro-prodrugs L-lysine based for 5-aminosalicylic acid and 6-mercaptopurine colon specific release.
abstract: 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, Nɛ-feruloyl-S-(6-purinyl)-L-lysine and Nɛ-acryloyl-S-(6-purinyl)-L-lysine were synthesized and then characterized by FT-IR, (1)H-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, Nɛ-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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Trombino
authors.forename: Roberta
authors.initials: R
authors.lastname: Cassano
authors.forename: Alessia
authors.initials: A
authors.lastname: Cilea
authors.forename: Teresa
authors.initials: T
authors.lastname: Ferrarelli
authors.forename: Rita
authors.initials: R
authors.lastname: Muzzalupo
authors.forename: Nevio
authors.initials: N
authors.lastname: Picci
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D003106:Colon / Q000378:metabolism; D005750:Gastric Juice / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000494:pharmacology; D007419:Intestinal Secretions / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D015122:Mercaptopurine / Q000737:chemistry* / Q000494:pharmacology; D019804:Mesalamine / Q000737:chemistry*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008863:Microspheres; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D007166:Immunosuppressive Agents; D011355:Prodrugs; D017382:Reactive Oxygen Species; D019804:Mesalamine; D008315:Malondialdehyde; D015122:Mercaptopurine; D008239:Lysine