title: NO-NSAIDs: Gastric-sparing nitric oxide-releasable prodrugs of non-steroidal anti-inflammatory drugs.
abstract: Recently, a new class of nitric-oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) is being studied as 'Safe NSAIDs' because of their gastric-sparing properties. As an extension of our novel disulfide linker technology, we have designed, synthesized and evaluated novel NO-releasing NSAID prodrugs such as NO-Aspirin (1b-d) and NO-Diclofenac (2b-c). Although the amide-containing derivative 1d did not show any bioavailability, the remaining compounds have shown fair to excellent pharmacokinetic, anti-inflammatory and gastric-sparing properties. Among them, however, the NO-Diclofenac (2b) has shown the most promising pharmacokinetic, anti-inflammatory and NO-releasing properties and protected rats from NSAID-induced gastric damage which could be attributable to the beneficial effects of NO released from these prodrugs.
authors.affiliation: Pharmacology Department, Piramal Life Sciences Limited, Nirlon Complex, Goregaon East, Mumbai 400 063, India.
authors.forename: Kumar V S
authors.initials: KV
authors.lastname: Nemmani
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Mali
authors.forename: Namdev
authors.initials: N
authors.lastname: Borhade
authors.forename: Asif R
authors.initials: AR
authors.lastname: Pathan
authors.forename: Manoj
authors.initials: M
authors.lastname: Karwa
authors.forename: Venu
authors.initials: V
authors.lastname: Pamidiboina
authors.forename: S P
authors.initials: SP
authors.lastname: Senthilkumar
authors.forename: Machhindra
authors.initials: M
authors.lastname: Gund
authors.forename: Arun K
authors.initials: AK
authors.lastname: Jain
authors.forename: Naveen K
authors.initials: NK
authors.lastname: Mangu
authors.forename: Nauzer P
authors.initials: NP
authors.lastname: Dubash
authors.forename: Dattatraya C
authors.initials: DC
authors.lastname: Desai
authors.forename: Somesh
authors.initials: S
authors.lastname: Sharma
authors.forename: Apparao
authors.initials: A
authors.lastname: Satyam
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001241:Aspirin / Q000737:chemistry / Q000494:pharmacology*; D004008:Diclofenac / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013270:Stomach / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D004008:Diclofenac; D009569:Nitric Oxide; D001241:Aspirin