NO-NSAIDs: Gastric-sparing nitric oxide-releasable prodrugs of non-steroidal anti-inflammatory drugs.
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.
Nemmani
Kumar V S
KV
Pharmacology Department, Piramal Life Sciences Limited, Nirlon Complex, Goregaon East, Mumbai 400 063, India.
Mali
Sunil V
SV
Borhade
Namdev
N
Pathan
Asif R
AR
Karwa
Manoj
M
Pamidiboina
Venu
V
Senthilkumar
S P
SP
Gund
Machhindra
M
Jain
Arun K
AK
Mangu
Naveen K
NK
Dubash
Nauzer P
NP
Desai
Dattatraya C
DC
Sharma
Somesh
S
Satyam
Apparao
A
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*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D004008:Diclofenac; D009569:Nitric Oxide; D001241:Aspirin