Abstract
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•Isatinimino acridinedione heterocyclic hybrids has been synthesized.•In silico docking capability was studied with 5F19 receptor.•In vivo antiinflammatory biological experiment has been done.•Carrageenan induced hind paw oedema was done with various factors.
A potent Nonsterodial Anti-inflammatory Drug (NSAID) candidates has been conceived and built by an assembly of a hydrophilic, fluorescent and COX-2 inhibiting units in the same molecule. The isatinimino-acridinedione core (TM-7) was achieved in a simple three step synthetic procedure viz (i) a multicomponent reaction between dimedone, aldehyde and amine to furnish the nitroacridinedione (4), (ii) reduction step and (iii) schiff’s-base condensation with isatin. The excellent anti-inflammatory pharmacological efficiency of the drug was established by in vivo biological experiments. Accordingly, it was found that the treatment with the synthesized isatinimino analogues (dosage: 30 mg/kg) inhibited protein expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) as well as production of prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6) levels induced by carrageenan. Further, a comparative molecular modeling analysis of TM-7 carried out with the crystal structure of aspirin acetylated human COX-2 suggested effectively binding and efficient accommodation inside the active site’s gorge.