title: Azo reductase- activated colon- targeting prodrugs of aminosalicylates for inflammatory bowel disease: preparation, pharmacokinetic and pharmacodynamic profile.
abstract: Azo prodrugs of aminosalicylates viz: 5-aminosalicylic acid and 4-aminosalicylic acid were synthesised using phenols as colon- targeting carriers for management of inflammatory bowel disease. The structures were confirmed by spectral and elemental analysis. These azo- linked prodrugs showed increased hydrophilicity which prevented their absorption from the upper GIT thus delivering them intact to the colon. They were also seen to be stable in stomach and intestinal homogenates, showing minimal release. Activation of prodrugs was faster in cecal matter showing upto 96-98% release with prolonged half lives. Amongst the azo series; 5-Aβ and 4-Ares significantly attenuated the symptoms of colitis induced by TNBS but their overall efficacy was less than SLZ. Safety assessment revealed absence of any abnormalities in hepatic and pancreas morphology with significantly low ulcerogenic propensity.
authors.forename: Dhaneshwar
authors.initials: D
authors.lastname: Suneela
authors.forename: Vadnerkar
authors.initials: V
authors.lastname: Gaurav
authors.affiliation: Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune-411 038, Maharashtra, India. suneeladhaneshwar@rediffmail.com.
authors.forename: Soares
authors.initials: S
authors.lastname: Samuel
mesh_terms: D010131:Aminosalicylic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001391:Azo Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007408:Intestinal Absorption / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009601:Nitroreductases; D010179:Pancreas / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001391:Azo Compounds; D011355:Prodrugs; D010131:Aminosalicylic Acid; D009247:NADH, NADPH Oxidoreductases; D009601:Nitroreductases; C021106:azoreductase