Background: :
A new series of O-benzyloximes derived from eugenol was synthesized
and was evaluated for its antinociceptive and anti-inflammatory properties.
Methods: :
The target compounds were obtained in good global 25-28% yields over 6 steps, which
led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4-
(methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4-
bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4-
(methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes.
Results::
These compounds have significant analgesic and anti-inflammatory effects, as evidenced
by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin
test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities
and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory
effects, exceeding the standard drugs indomethacin and celecoxib.
Conclusion: :
Molecular docking studies have provided additional evidence that the pharmacological
profile of these compounds may be related to inhibition of COX enzymes, with slight preference for
COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive
prototypes, with a novel structural pattern capable of being explored in further studies aiming at
their optimization and development as drug candidates.
Inhibitory Effects of Auraptene and Naringin on Astroglial Activation, Tau Hyperphosphorylation, and Suppression of Neurogenesis in the Hippocampus of Streptozotocin-Induced Hyperglycemic Mice