Abstract:
Five new series of hydroxybenzofuranyl-pyrazolyl chalcones 3a,b, hydroxyphenyl-pyrazolyl chalcones
6a–c and their corresponding pyrazolylpyrazolines 4a, d, 7a–c and 8a–f have been synthesized and evaluated
for their in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity. All the synthesized compounds ex-
hibited dual COX-1 and COX-2 inhibitory activity with obvious selectivity against COX-2. The pyrazolylpyr-
azolines 4a–d and 8a–f bearing two vicinal aryl moieties in the pyrazoline nucleus showed more selectivity
towards COX-2. Within these two series, derivatives 4c, d and 8d–f bearing the benzenesulfonamide group
were the most selective. Compounds 4a–d and 8a–f were further subjected to in vivo anti-inflammatory
screening, ulcerogenic liability and showed good anti-inflammatory activity with no ulcerogenic effect. In
addition compounds 4c and 8d as examples showed prostaglandin (PG)E2 inhibition % 44.23 and 51.4 re-
spectively, tumor necrosis factor α (TNFα) inhibition % 33.48 and 41.41 respectively and gastroprotective
effect in ethanol induced rodent gastric ulcer model. In addition, to explore the binding mode and selectivity
of our compounds, 8d and celecoxib were docked into the active site of COX-1 and COX-2. It was found that
compound 8d exhibited a binding pattern and interactions similar to that of celecoxib with COX-2 active site,
while bitter manner of interaction than celecoxib to COX-1 active site.
