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.
Design, Synthesis and Anti-inflammatory Activity of Structurally Simple Anthranilic Acid Congeners Devoid of Ulcerogenic Side Effects
