Background: Furanone and pyrrolone heterocyclic ring system represent important
and interesting classes of bioactive compounds. Medicinal chemists use these heterocycyclic
moieties as scaffolds in drug design and discovery.
Methods: A series of 3-arylidene-5-(naphthalene-2-yl)-furan-2(3H)-ones (2a-j) were synthesized
by incorporating pharmacophore of COX-2 inhibitor rofecoxib and naphthyl ring of
naproxen as potential non steroidal anti-inflammatory agents. These furanone derivatives
were subsequently reacted with dry ammonia gas and benzylamine to furnish corresponding
3-arylidene-5-(naphthlen-2-yl)-1H-pyrrol-2(3H)-ones (3a-e) and 3-arylidene-1-benzyl-5-
(naphthalene-2-yl)-1H-pyrrol-2(3H)-ones (4a-e), respectively. The newly prepared heterocyclics
were screened for their expected in-vivo biological activities including anti-inflammatory,
analgesic and ulcerogenic actions in rodents. The COX-2 inhibitory behavior of synthesized
compounds was also assessed via automated docking studies.
Results: The chemical structure of the synthesized compounds was characterized by using
modern spectroscopic techniques. Result of in-vivo pharmacological studies demonstrated
that almost all N-Benzyl-pyrrol-2(3H)-ones (4a-e) showed better anti-inflammatory and analgesic
activities in comparison with the other two series of furan-2(3H)-ones and pyrrol-
2(3H)-ones. The moldock score value of the tested compounds was found in the range of
-116.66 to -170.328 and was better than the standard drug.
Conclusion: Among all the synthesized compounds, only nine compounds (2d, 2g, 2h, 3d,
4a, 4b, 4c, 4d and 4e) exhibited potent anti-inflammatory and analgesic activities with significantly
reduced gastrointestinal toxicity in various animal models in comparison to standard
drug, diclofenac. Therefore, it is recommended to explore the potential of the synthesized
compounds as lead candidates for the development of new therapeutic agents.